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Title
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SIGNATURE PAGE
Bhaskar Reddy
Manager, Quality Assurance QUALITY CONTROL-TR-OHM LABS 02-Jan-2018 Reviewed and Approved By
Bhupendra
Patel Senior Director, Quality Assurance QUALITY ASSURANCE-TR-OHM 03-Jan-2018 Reviewed and Approved By
LABS
This document was approved and signed electronically and this is the manifestation of the
electronic signature.
Title : DISPERSION
Method A: For Opadry Powder (Dry Dispersion coating systems (Dry Dispersions –
Film Coating Systems))
1. Place about 100 g of powder sample onto a 600 micrometer testing sieve
(U.S. #30 Standard).
Retained Material:
Particles should be small, soft, and uniform in size and break up easily with
pressure applied with fingertip.
GENERAL PROCEDURE
Document No. : GP000189
Version No. : 5.0; Effective
Effective Date : 04-Jan-2018
Review Due : 02-Jan-2021
Title : DISPERSION
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1. Place about 50 g of powder sample onto a 600 µm testing sieve (U.S. Sieve No. 30).
Manually shake the sieve, allowing powder to fall through. Examine the retained material.
2. Pour approximately 10 g of the blend onto a piece of white paper (or paper towel). Using
a spatula spread it over the paper towel or white piece of paper, examining for pigment
specks or streaks.
3. Using a spatula, spread it over the paper, examining for pigment specks or streaks
No specks: PASS
Specks observed: FAIL
Batch requires additional processing
4. Where doubt exists for any of these tests, review product history and/or evaluate
previously acceptable batches.
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Method D For Product line 21s, 24k, 21A540005 (Colorcon D10 procedure):
1. Place about 100 g of powder sample onto a 600 micrometer testing sieve
(U.S. #30 Standard).
Retained Material:
5. Particles should be small, soft, and uniform in size and break up easily with pressure
applied with fingertip.
6. Hard pieces does not breakup easily, should dissolve in Methylene chloride or
Anhydrous Ethanol.
HISTORY OF CHANGES
CC058321 GP000189 Ver. 3.0 Method D added for For Product line 21s,
24k, 21A540005.
:
Title
:
SIGNATURE PAGE
Dalvinder Singh
QC Senior Manager, Raw Materials QUALITY CONTROL-LA-OHM LABS 13-Jun-2016 Reviewed and Approved By
Gira Shah
QA Group Leader, Documentation QUALITY ASSURANCE-TR-OHM LABS 14-Jun-2016 Reviewed and Approved By
This document was approved and signed electronically and this is the manifestation of the
electronic signature.
Procedure:
Ignite the clean suitable crucible (silica, platinum, quartz or porcelain) at 600 ± 50° C for
30 min, allow to cool in a desiccator (silica gel or other suitable desiccant), then weigh.
Record the weight (W1).
Weigh accurately 1-2 g of the substance (W), or the amount specified in the individual
monograph in the crucible. Record the weight.
GENERAL PROCEDURE
Document No. : GP000141
Version No. : 4.0; Effective
Effective Date : 16-Jun-2016
Review Due : 15-Jun-2019
Title : RESIDUE ON IGNITION/SULFATED ASH
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Cool the crucible in a desiccator (over silica gel or other suitable desiccant), weigh, record the
weight (W2) and calculate the percentage of residue.
Unless otherwise specified, if the amount of the residue so obtained exceeds the limit
specified in the individual monograph, repeat moistening with Sulfuric acid, heating and
ignition as before, using a 30 minute ignition period until two successive weighing do not differ
by more than 0.5 mg or until the percentage of residue complied with the limit prescribed in the
individual monograph. Note the final weight. (W2).
Sulfated ash /
(W2 – W1)
Residue on ignition = × 100
(% w/w) W
Where:
Calibration of the muffle furnace may be carried out using an appropriate digital temperature
meter and a working thermocouple probe calibrated against a standard thermocouple
traceable to the National Institute of Standards and Technology.
Verify the accuracy of the measuring and controlling circuitry of the muffle furnace by checking
the positions in the furnace at the control set point temperature of intended use. Select
positions that reflect the eventual method of use with respect to location of the specimen
under test. The tolerance is ± 25°C at each position measured.
Precautions:
5. Sulfuric acid used should be AR grade and free from any contamination.
7. Conduct the ignition at a temperature to affect the complete combustion of the carbon
without sample spill out.
9. Use heat resistant gloves while placing and removing the crucible from the muffle
furnace.
HISTORY OF CHANGES
:
Title
:
SIGNATURE PAGE
Hemendra Makwana
Manager - Quality Control - OSD - Dewas QC OSD - DEWAS 08-Nov-2017 Reviewed and Approved By
Raju Naik
Senior Executive-Quality Assurance-Goa QUALITY CONTROL PHARMA – GOA 08-Nov- Reviewed and Approved By
2017
GENERAL PROCEDURE
Document No. : GP000083
Version No. : 4.0; Effective
Effective Date : 02-Dec-2017
Review Due : 30-Nov-2020
Title : IODINE VALUE
Procedure:
USP METHODS
Unless otherwise specified in the individual monograph, use the following quantity of the
substance being examined.
Iodine Weight in g,
value ± 0.1
expecte
<5 3.0
5-20 1.0
21-50 0.4
51-100 0.2
101-150 0.13
151-200 0.1
Procedure
1. Unless otherwise specified, weigh accurately the quantity of the substance being
examined, stated as above table. Place it in a dry 250-mL Iodine flask. Add 10 mL of
Chloroform and dissolve.
2. Add slowly 25 mL of Iodobromide TS insert the stopper and allow to stand in the dark
for 30 min, unless otherwise specified in the monograph, shaking frequently.
3. Add 30 mL of Potassium iodide TS and 100 mL of water and titrate with 0.1 M Sodium
thiosulphate using starch TS, added towards the end of titration as indicator. Note the
number of mL required (a).
4. Carry out the operation in exactly the same manner, but without the substance being
examined. Note the number of mL required (b).
Calculations
(b-a) x 1.269 x M
Iodine value = -----------------------
W x 0.1
Where
Note
If more than half of the Iodobromide TS is absorbed by the portion of the sample taken,
repeat the determination using a smaller portion of sample under examination.
THIS IS A PRINTED COPY OF AN ELECTRONIC DOCUMENT. PLEASE CHECK ITS VALIDITY
METHOD II
Unless otherwise specified in the individual monograph, use the following quantity of the
substance being examined.
Iodine Weight in g,
value ± 0.1
expecte
<5 3.0
5-20 1.0
21-50 0.4
51-100 0.2
101-150 0.13
151-200 0.1
Procedure
1. Melt the sample, if it is not already liquid. (Note: - The temperature during melting
should not exceed the melting point of the sample solution by more than 10°C).
2. Pass through two pieces of filter paper to remove any solid impurities and the last
traces of moisture. The filtration may be performed in an air oven at 100 °C but should
be completed within 5 min ± 30 sec. The sample must be absolutely dry. All
glassware must be absolutely clean and completely dry.
3. After filtration, allow the filtered sample to achieve a temperature of 68 °C to 71 ± 1 °C
before weighing the sample. Once the sample has achieved a temperature of 68 °C to
71 ± 1°C, immediately weigh the sample into a 500-mL Iodine flask, using the weights
and weighing accuracy noted in the accompanying table.
4. Add 15 mL of a mixture of fresh cyclohexane and Acetic acid (1:1), and swirl to
dissolve the sample.
5. Add 25.0 mL of Iodochloride TS, insert the stopper securely in the flask, and swirl to
mix. Allow it to stand at 25 ± 5 °C, protected from light, with occasional shaking, for
1.0 h. or 2.0 h. (If the Iodine value is less than 150, then shake for 1.0 h, if Iodine value
is equal or more than 150 then shake for 2.0 h). Then, within 3 min after the indicated
reaction time, add, in the order named, 20 mL of Potassium iodide solution(10 % w/v)
and 150 mL of recently boiled and cooled water, and mix.
6. Within 30 min, titrate the liberated Iodine with 0.1 M Sodium thiosulfate, while stirring
by Mechanical means after each addition of thiosulfate. When the yellow Iodine color
has almost disappeared, add 1 - 2 mL of Starch indicator solution, and continue the
titration with 0.1 M Sodium thiosulfate until the blue color is discharged.
7. Perform a blank test at the same time with the same quantities of the same reagents
and in the same manner.
Calculations
V x 1.269 x M
Iodine value = ------------------
w x 0.1
Where
Note: The weight of the substance must be such that there will be an excess of
Iodochloride TS of 50 - 60 % of the amount added, that is, 100 % to 150 % of the amount
absorbed).
METHOD A
Unless otherwise specified in the individual monograph, use the following quantity of the
substance being examined.
< 20 1.0
20 – 60 0.5 - 0.25
60 – 100 0.25 - 0.15
> 100 0.15 - 0.10
Procedure
1. Unless otherwise specified, weigh accurately the quantity of the substance being
examined, stated as above table. Place it in a dry 250-mL Iodine flask which is dry or
has been rinsed with glacial Acetic acid and add 15 mL of Chloroform and dissolve
unless otherwise specified in the monograph.
2. Add slowly 25 mL of Iodine bromide solution (2 % w/v in glacial acetic acid). Insert the
stopper and allow to stand in the dark for 30 min, unless otherwise specified in the
monograph, shaking frequently.
3. Add 10 mL of Potassium iodide 100 g / 1000 mL solution and 100 mL of water and
titrate with 0.1 M Sodium thiosulphate. Shaking vigorously until the yellow colour is
almost discharged. Add 5 mL of starch solution and continue the titration adding the
0.1 N sodium thiosulphate dropwise until the colour is discharged. Note the number of
mL required (a).
4. Carry out the operation in exactly the same manner, but without the substance being
examined. Note the number of mL required (b).
Calculations
(b-a) x 1.269 x M
Iodine value = -----------------------
W x 0.1
Where
Method B
Procedure
1. Unless otherwise specified, weigh accurately the quantity of the substance being
examined, stated in the below Table. Place it in a dry 250-mL Iodine flask fitted with a
ground stopper and which is dry or has been rinsed with glacial Acetic acid. Add 15 mL
of mixture of equal volume of Cyclohexane & glacial acetic acid and dissolve unless
otherwise specified in the monograph. If necessary, melt the substance before
dissolution (melting point greater than 50 °C).
2. Add very slowly the volume of Iodine Chloride solution (1.4 % w/v solution in glacial
acetic acid) stated in the above table. Close the flask and keep it in the dark for 30 min,
unless otherwise prescribed. Shaking frequently.
3. Add 10 mL of Potassium iodide 100 g / 1000 mL solution and 100 mL of water and
Titrate with 0.1 M sodium thiosulphate , shaking vigorously until the yellow colour is
almost discharged. Add 5 ml of starch solution and continue the titration adding the
0.1 M sodium thiosulphate dropwise until the colour is discharged. Note the number of
mL required (a).
4. Carry out the operation in exactly the same manner, but without the substance being
examined. Note the number of mL required (b).
Calculations
(b-a) x 1.269 x M
Iodine value = -----------------------
w x 0.1
Where
1. Dissolve the specified quantity of the substance being examined, accurately weighed, in
10 mL of dichloromethane in a dry 250 mL Iodine flask.
2. Add 20.0 mL of Iodine monochloride solution, insert the stopper, previously moistened
with dilute Potassium iodide solution(10 % w/v), and allow to stand in the dark at 15 °C
to 25 °C for 30 min.
3. Place 15 mL of dilute Potassium iodide solution(10 % w/v) in the cup top, carefully
remove the stopper, rinse the stopper and the sides of the flask with 100 mL of water,
shake and titrate with 0.1 M Sodium thiosulphate using starch mucilage, added towards
the end of the titration, as indicator. Note the number of mL required (a).
4. At the same time carry out the operation in exactly the same manner, but without the
substance being examined. (Blank titration). Note the number of mL required (b).
Calculations
(b-a) x 1.269 x M
Iodine value = -----------------------
w x 0.1
Where
NOTES
Procedure
1. Dissolve the specified quantity of the substance being examined, accurately weighed, in
10 mL Carbon tetrachloride in a dry 500 mL Iodine flask.
2. Add 20.0 mL of Iodine monochloride solution, insert the stopper and allow to stand in the
dark at 15 °C to 25 °C for 30 min.
3. Place 15 mL of Potassium iodide solution(16.6% w/v) in the cup top, carefully remove
the stopper, rinse the stopper and the sides of the flask with 100 mL of water, shake and
titrate with 0.1 M Sodium thiosulphate using starch solution, added towards the end of
the titration, as indicator. Note the number of mL required (a).
4. At the same time carry out the operation in exactly the same manner, but without the
substance being examined. (Blank titration). Note the number of mL required (b).
Calculations
(b-a) x 1.269 x M
Iodine value = -----------------------
w x 0.1
Where
NOTES
Unless otherwise specified in the individual monograph, use the following quantity of the
substance being examined.
Procedure
1. Unless otherwise specified, weigh accurately the quantity of the substance being
examined, stated as above.Place it in a dry 300 mL Iodine flask which is dry or has
been rinsed with glacial Acetic acid unless otherwise specified in the monograph. Add
15 mL of Chloroform and dissolve.
2. Add slowly from a burette 25 mL of Iodine bromide solution. Insert the stopper and
allow to stand in the dark for 30 min, unless otherwise specified in the monograph,
shaking frequently.
3. Add 10 mL of Potassium iodide solution (16.6 % w/v) and 100 mL of water and titrate
with 0.1 M Sodium thiosulphate using starch solution, added towards the end of
titration as indicator. Note the number of mL required (a).
4. Carry out the operation in exactly the same manner, but without the substance being
examined. Note the number of mL required (b).
Calculations
(b-a) x 1.269 x M
Iodine value = -----------------------
W x 0.1
THIS IS A PRINTED COPY OF AN ELECTRONIC DOCUMENT. PLEASE CHECK ITS VALIDITY
Where
Procedure
Calculations
(b-a) x 1.269 x M
Iodine value = -----------------------
w x 0.1
Where
Page No:
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Note
HISTORY OF CHANGES
:
Title
:
SIGNATURE PAGE
Jignesh Soni
Associate Director QC 14-Nov- Reviewed and Approved By
2018
Bhupendra
Patel Senior Director, Quality Assurance QUALITY ASSURANCE-TR-OHM Reviewed and Approved By
LABS 15-Nov-2018
This document was approved and signed electronically and this is the manifestation of the
electronic signature.
GENERAL PROCEDURE
Document No. : GP000054
Version No. : 8.0; Effective
Effective Date : 16-Nov-2018
Review Due : 14-Nov-2021
Title : DESCRIPTION
Title : DESCRIPTION
Procedure:
ODOR
1. Examine a sample of not more than 25 g immediately after opening the package.
2. If any odor is perceptible, transfer the sample rapidly to an open container and
re-examine after 15 min.
3. If the odor is still there, the sample does not comply with the description odorless.
NOTE: The terms ‘odorless’ or ‘practically odorless’ or ‘faint’ characteristics odor are
descriptive only and are not to be regarded as standards of purity for a particular lot of
an article, except in those cases where a particular odor is specifically prohibited in the
monograph under ‘standards’.
The flavors may be checked by comparing it with the latest approved batch kept in a
well closed container.
TASTE
Statements on taste are provided only in cases where this property is a guide to the
acceptability of the material. Such statements are not part of the official standards.
COLOR
1. The test for color may be checked by spreading the material/powder/beads under test on
a clean butter paper in a well illuminated area and may be compared with the color of
the last / previously approved batch / lot or checked with the unaided eyes.
2. Any variation may be noted down and reported.
3. The color of the solvents may also be checked by taking the sample in a clean
stoppered test tube.
4. White color may be checked against a black background and black and other colors may
be checked against white background.
Quantity of the dosage units shall be taken for description as per below table.
Table
Note: Description can be checked during execution of other tests also e.g. Average
weight, Viscosity etc. and less quantity also can be used for description test based on
availability of dosage units.
TABLETS
A. UNCOATED/CORE TABLETS
1. Observe the shape, nature of the edges, scoring, color and imprints of a representative
sample.
2. In case of uncoated tablets, also observe the presence of foreign matter, sticking,
chipping, capping, mottling and color uniformity.
3. The color of the tablets should match the current color shade requirements. The color of
a previously approved batch may be taken as a reference.
1. Observe and record the nature of tablets, shape, shine, color, color uniformity and
intactness (batch to batch and within the batch).
1. Observe and record the nature of tablets, shape, shine, color, color uniformity and
intactness (batch to batch and within the batch).
CAPSULE
1. Observe the color combination of cap and body, color of imprints on cap and body, self-
locking, size and any abnormality.
2. Open capsules and collect the powder on a clean white paper and record the color and
nature of the powder.
B. SOFT GELATIN CAPSULES
Observe, record and report the color, imprints, shape and any abnormality. Open capsules
and record the color and nature of the collected semi-solid mass.
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1. Take out the contents from the dry syrup bottles and report the color, flavor and nature
of the powder.
2. Reconstitute as directed on the label and report its nature, color, suspendibility, taste
and flavor.
LIQUID ORALS
1. Observe and note the description of the oral liquid preparation (clear liquid; syrupy
liquid; suspension), color of the liquid, taste and flavor of the liquid.
2. For description and color of the liquid observation is done by pouring out adequate
quantity from a bottle to a clean and dry transparent glass container (test tube, or
beaker).
INJECTIONS
A. AMPOULES
Take out the contents from the ampoule and transfer into a clean dry test tube. Observe
and record the nature, color and foreign particles, if any.
B. VIALS
1. Take out the contents from the vial on a white paper and observe the nature and color
of the powder.
2. Reconstitute the injection in a vial by injecting a quantity of water for injection as
specified for the product in the pharmacopeia or in the directions for use.
3. Observe and record the solubility, color and nature of solution or suspension.
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INTRAMAMMARY INJECTION
Take out the contents of a disposable syringes on a butter paper and record the apparent
consistency, transparency or translucency, color and grittiness.
OINTMENT
Take out the contents of a collapsible tubes, bottles / jars or cartridges, on a butter paper
and record the apparent consistency, transparency or translucency, color and grittiness.
EYE DROPS
Shake and transfer the contents to a clean dry container and record the color, nature (clear
liquid / suspension) and presence of any suspended ingredients.
NOTE: The description for color, taste and odor may vary from person to person, however,
until there is significant difference, all the statements should be treated as same.
OPADRY’S
Perform the Film Formation test for both standard and sample. For the Description test,
compare the films of standard and sample.
REFERENCES
HISTORY OF CHANGES
HISTORY OF CHANGES
CCR Number Supersedes (Number Change(s) Made
and last version)
:
Title
:
SIGNATURE PAGE
Bhaskar Reddy
Manager, Quality Assurance QUALITY CONTROL-TR-OHM LABS 30-Jan-2018 Reviewed and Approved By
Gira Shah
Manager, Quality Assurance QUALITY ASSURANCE-TR-OHM LABS 30-Jan-2018 Reviewed and Approved By
This document was approved and signed electronically and this is the manifestation of the
electronic signature.
Printed By : Arti Printed Time (IST) : 13-Mar-2019 3:27 AM 1
Pandya
The signature page is the first page of this document
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GENERAL PROCEDURE
Document No. : GP000046
Version No. : 7.0; Effective
Effective Date : 01-Feb-2018
Review Due : 30-Jan-2021
Title : MICROBIAL ENUMERATION TESTS AND TESTS FOR SPECIFIED
MICROORGANISMS
2.0 OBJECTIVE
3.0 SCOPE
This procedure is used for testing raw materials, finished products, intermediates and
drug substance or excipients for Total Aerobic microbial count (TAMC), Total
combined Molds and Yeasts count (TYMC) and for the presence of Staphylococcus
aureus, Pseudomonas aeruginosa, Salmonella species, Escherichia coli, Candida
albicans and Bile tolerant Gram negative bacteria. In accordance with the
harmonized USP Microbiological Examination of Non sterile Products: ‘Microbial
Enumeration Tests’ referenced in USP <61>, Tests for ‘Specified Microorganisms’
referenced in USP <62>, and the ‘Acceptance Criteria of Pharmaceutical
Preparations and Substances for Pharmaceutical Use, referenced in USP <1111>.
4.0 RESPONSIBILITY
4.1. All microbiologists shall be responsible for testing all test samples per
this procedure
5.1 PROCEDURE
5.2. SAFETY:
5.3. EQUIPMENT:
5.4.1.CULTURE MEDIA
5.4.2. REAGENTS
5.5.1. The media required in this procedure are made from the
ingredients listed herein.
A
Buffered Sodium Chloride-Peptone Solution pH 7.0
Potassium Dihydrogen Phosphate 3.6 g
Disodium Hydrogen Phosphate Dihydrate 7.2 g t 0.06 M
(equivalent o 7
Sodium Chloride phosphate)
4.3 g
Peptone (meat or casein) 1.0 g
Purified Water 1000 mL
Adjust the pH so that after sterilization it is 7.0 at 25 °C. Sterilize in an autoclave using a
validated cycle
B
Stock Buffer Solution
Transfer 34.0g of potassium dihydrogen phosphate to a 1000-mL volumetric
flask, dissolve in 500 mL of purified water, adjust with sodium hydroxide to a
pH of 7.2 ±0.2, add purified water to volume, and mix. Dispense in containers,
and sterilize in an autoclave, using a validated cycle. Store at a temperature of
2°C to 8°C
C
Phosphate Buffer Solution pH 7.2
Prepare a mixture of Purified Water and Stock Buffer Solution (800:1 v/v), and
sterilize
D
Soybean-Casein Digest Agar (SCDA or TSA)
Pancreatic digest of Casein 15.0 g
Papaic Digest of Soya bean meal 5.0 g
Sodium chloride 5.0 g
Agar 15.0 g
Purified Water 1000 mL
Sterilize in an autoclave using a validated cycle. Adjust pH so that after sterilization it is
7.3 ± 0.2 at 25 °C or according to Manufacturer’s label
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E
Soybean Casein Digest Agar with 4 % Polysorbate 20 (Tween 20)
and 0.5 % Lecithin (*SCDA or *TSA)”
Pancreatic digest of Casein 15.0 g
Papaic Digest of Soya bean meal 5.0 g
Sodium chloride 5.0 g
Agar 15.0 g
Purified Water 960 mL
4 % Tween 20 40 mL
0.5% % Lecithin 5.0 g
Adjust pH so that after sterilization, it is 7.3 ± 0.2 at 25°C or according to Manufacturer’s
label. Autoclave using a validated cycle.
F
Soybean-Casein digest Broth (SCD or TSB)
Pancreatic digest of Casein 17.0 g
Papaic Digest of Soybean 3.0 g
Sodium chloride 5.0 g
Dibasic Potassium Phosphate 2.5 g
Dextrose 2.5 g
Purified Water 1000mL
Adjust the pH so that after sterilization it is 7.3 ± 0.2 at 25°C or according to
manufacturer’s label. Sterilize in an autoclave using a validated cycle.
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G
Soybean Casein Digest Broth with 4 % Polysorbate 20 and 0.5 %
Lecithin (*SCB or *TSB)
Pancreatic digest of Casein 17.0 g
Papaic Digest of Soybean 3.0 g
Sodium chloride 5.0 g
Dibasic Potassium Phosphate 2.5 g
Dextrose 2.5 g
4% Polysorbate 20 (tween 20) 40 mL
0.5 % Lecithin 5.0 g
Purified Water 960 mL
Adjust the pH so that after sterilization it is 7.3 ± 0.2 at 25°C or according to the
manufacturer’s label. Sterilize in an autoclave using a validated cycle
H
Sabouraud Dextrose Broth (SDB)
Mixture of Peptic Digest of Animal Tissue 10.0 g
and Pancreatic Digest of Casein (1:1)
Dextrose 20.0 g
Purified Water 1000 mL
Adjust the pH so that after sterilization it is 5.6 ± 0.2 or according to manufacturer’s label.
Sterilize in an autoclave using a validated cycle.
I
Sabouraud Dextrose Agar (SDA)
Mixture of Peptic Digest of Animal Tissue 10.0 g
and Pancreatic Digest of Casein (1:1)
Dextrose 40.0 g
Agar 15.0 g
Purified Water 1000 mL
Adjust the pH so that after sterilization it is 5.6 ± 0.2 at 25°C or according to the
manufacturer’s label. Sterilize in an autoclave using a validated cycle.
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J
Sabouraud Dextrose Agar with 0.05g (50.0 mg)
Chloramphenicol (SDA+)
Dextrose 40 g
Mixture of equal parts of peptic
Digest of animal tissue and 10 g
pancreatic digest of Casein
Agar 15 g
Lecithin 5g
Chloramphenicol 0.05 g
Purified Water 1000 mL
Add 0.05 g of Chloramphenicol to each 1000 mL of re-hydrated medium. Heat to boiling.
Adjust the pH so that after sterilization it is 5.6 ± 0.2. at 25°C or according to the
manufacturer’s label. Sterilize in an autoclave using a validated cycle.
K
Enterobacteria Enrichment Broth Mossel
Pancreatic Digest of Gelatin 10.0 g
Glucose Monohydrate 5.0 g
Dehydrated Ox Bile 20.0 g
Potassium Dihydrogen Phosphate 2.0 g
Disodium Hydrogen Phosphate Dihydrate 8.0 g
Brilliant Green 15 mg
Purified water 1000 mL
Adjust the pH so that after heating it is 7.2 ±0.2 at 25 °C. Heat at 100°C for 30 minutes
and cool immediately.
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L
Violet Red Bile Glucose Agar (VRBGA)
Pancreatic Digest of Gelatin 7.0 g
Yeast Extract 3.0 g
Bile Salts 1.5 g
Sodium Chloride 5.0 g
Glucose Monohydrate 10.0 g
Agar 15 0 g
Neutral Red 30 mg
Crystal Violet 2 mg
Purified water 1000 mL
Adjust pH so that after heating it is 7.4 ± 0.2 at 25 °C or according to the manufacturer’s
label. Heat to boiling; do not heat in an autoclave.
M
MacConkey Agar (MCA)
Pancreatic digest of Gelatin 17.0 g
Peptone (meat and Casein) 3.0 g
Lactose (Lactose Monohydrate) 10.0 g
Sodium chloride 5.0
Bile salts 1.5 g
Agar 13.5 g
Neutral red 3.0 mg
Crystal violet 1 mg
Purified Water 1000 mL
Adjust pH so that after sterilization it is 7.1± 0.2 at 25°C or according to the
manufacturer’s label. Sterilize in an autoclave using a validated cycle.
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N
MacConkey Broth (MCB)
Pancreatic digest of Gelatin 20.0 g
Lactose 10.0 g
Dehydrated Ox Bile (Oxgall) 5.0 g
Bromocresol Purple 10 mg
Purified water 1000 mL
Adjust the pH so that after sterilization, it is 7.3 at 25°C. Sterilize in an autoclave
using a validated cycle.
O
Rappaport Vassiliadis Salmonella Enrichment Broth (RVSEB)
Soya Peptone 4.5 g
Magnesium Chloride Hexahydrate 29.0 g
Sodium Chloride 8.0 g
Dipotassium Phosphate 0.4 g
Potassium Dihydrogen Phosphate 0.6 g
Malachite Green 0.036 g
Purified Water 1000 mL
Dissolve by warming slightly. Sterilize in autoclave using validated cycle. Adjust the pH
so that after heating and sterilization, it is 5.2±0.2 at 25°C or according to the
manufacturer’s label.
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P
Xylose Lysine Deoxycholate (XLD) Agar
Xylose 3.5 g
L-Lysine 5.0 g
Lactose (Lactose Monohydrate) 7.5 g
Sucrose 7.5 g
Sodium chloride 5.0 g
Yeast extract 3.0 g
Phenol red 80 mg
Agar 13.5 g
Sodium Deoxycholate 2.5 g
Sodium Thiosulfate 6.8 g
Ferric Ammonium Citrate 0.8 g
Purified water 1000 mL
Adjust pH so that after heating it is 7.4 ± 0.2 at 25°C or according to the manufacturer’s
label. Heat just to boil, cool to 50°C in a water bath and pour into Petri dishes. Do not
heat in an autoclave.
Q
Cetrimide (CET) Agar
Pancreatic digest of gelatin 20.0 g
Magnesium Chloride 1.4 g
Potassium sulfate 10.0 g
Agar 13.6 g
Cetrimide 0.3 g
Glycerol 10.0 mL
Purified Water 1000 mL
Add 10 mL of Glycerol in a liter of the solution. Heat to boiling for 1 minute with shaking.
Adjust the pH so that after sterilization it is 7.2±0.2 at 25°C or according to
manufacturer’s label. Sterilize in an autoclave using a validated cycle.
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R
Mannitol Salt Agar
Pancreatic digest of Casein 5.0 g
Peptic digest of Animal Tissue 5.0 g
Beef extract 1.0 g
Sodium Chloride 75.0 g
D- Mannitol 10.0 g
Phenol red 0.025 g
Agar 15.0 g
Purified Water 1000 mL
Heat to boiling for 1 minute with shaking. Adjust the pH so that after sterilization it is
7.4 ± 0.2. at 25 °C or according to the manufacturer’s label. Sterilize in an autoclave
using a validated cycle.
S
Potato Dextrose Agar
Infusion from potatoes 200 g
Dextrose 20.0 g
Agar 15.0 g
Purified Water 1000 mL
Adjust the pH so that after sterilization it is 5.6±02 at 25 °C or according to
manufacturer’s label. Sterilize in an autoclave using a validated cycle
GENERAL PROCEDURE
Document No. : GP000046
Version No. : 7.0; Effective
Effective Date : 01-Feb-2018
Review Due : 30-Jan-2021
Title : MICROBIAL ENUMERATION TESTS AND TESTS FOR SPECIFIED
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MICROORGANISMS
GENERAL PROCEDURE
Document No. : GP000046
Version No. : 7.0; Effective
Effective Date : 01-Feb-2018
Review Due : 30-Jan-2021
Title : MICROBIAL ENUMERATION TESTS AND TESTS FOR SPECIFIED
MICROORGANISMS
Page No:
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GENERAL PROCEDURE
Document No. : GP000046
Version No. : 7.0; Effective
Effective Date : 01-Feb-2018
Review Due : 30-Jan-2021
Title : MICROBIAL ENUMERATION TESTS AND TESTS FOR SPECIFIED
MICROORGANISMS
Page No:
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Psa-F Psa-P
Colony Morphology: Generally Greenish Generally greenish
to Yellow
Fluorescence in UV Yellow Blue
Light:
Note: If the colonies which have the characteristics listed in Section 5.7.2.2.8.3
(refer to Table)are present confirm the presence of Pseudomonas aeruginosa
with Oxidase test
5.7.2.2.9. OXIDASE TEST FOR CONFIRMATION OF
PRESENCE OF PSEUDOMONAS AERUGINOSA
GENERAL PROCEDURE
Document No. : GP000046
Version No. : 7.0; Effective
Effective Date : 01-Feb-2018
Review Due : 30-Jan-2021
Title : MICROBIAL ENUMERATION TESTS AND TESTS FOR SPECIFIED
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MICROORGANISMS
5.8. Report:
Use the report format as per Attachment IV to report the test results.
6.0 ATTACHMENTS:
ATTACHMENT I
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ATTACHMENT II
ATTACHMENT II (Continued)
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ATTACHMENT III
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ATTACHMENT IV
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GENERAL PROCEDURE
Document No. : GP000046
Version No. : 7.0; Effective
Effective Date : 01-Feb-2018
Review Due : 30-Jan-2021
Title : MICROBIAL ENUMERATION TESTS AND TESTS FOR SPECIFIED
MICROORGANISMS
ATTACHMENT V
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GENERAL PROCEDURE
Document No. : GP000046
Version No. : 7.0; Effective
Effective Date : 01-Feb-2018
Review Due : 30-Jan-2021
Title : MICROBIAL ENUMERATION TESTS AND TESTS FOR SPECIFIED
MICROORGANISMS
Page No:
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HISTORY OF CHANGES
:
Title
:
SIGNATURE PAGE
Aarohi Shah
QC Senior Chemist QUALITY CONTROL-TR-OHM LABS 06-Dec-2018 Reviewed and Approved By
Frank Piechota
Manager QA QA 06-Dec-2018 Reviewed and Approved By
Jignesh Soni
Associate Director QC 07-Dec- Reviewed and Approved By
2018
Gira Shah
Manager, Quality Assurance QUALITY ASSURANCE-TR-OHM 07-Dec- Reviewed and Approved By
LABS 2018
This document was approved and signed electronically and this is the manifestation of the
electronic signature.
2. SAFETY
Always observe safe laboratory practices. Consult the appropriate material safety
Data sheet (MSDS) before handling any chemical if you are unfamiliar with the
proper safety precautions.
3. PROCEDURE
GENERAL PROCEDURE
Document No. : GP000041
Version No. : 8.0; Effective
Effective Date : 11-Dec-2018
Review Due : 09-Dec-2021
Title : MICROBIOLOGICAL WATER TESTING
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The culture media required in this procedure are made from the ingredients
listed herein.
Enter the media, reagents and solutions information used for the testing in
the ATTACHMENT VI - MEDIA, REAGENTS, SOLUTIONS AND POSITIVE
CONTROL ORGANISMS TRACKING INFORMATION.
Yeast 3.0 g
Extract 7.0 g
Peptone 1.5 g
Bile salt 10.0 g
No.3 5.0 g
Lactose 15.0 g
Sodium 0.03 g
Chloride Agar 0.002 g
Neutral
Final pH 7.4 ± 0.2
Note for Potable water samples: Within one hour of receipt, treat
chlorinated samples (and other samples containing residual halogens) with
10% Sodium thiosulfate or sample directly into commercially available
Coliform containers. 0.1 mL of 10% Sodium thiosulfate per 120 mL of
sample is required. Mix well.
3.10.1.11. Count the total CFU from the plate and report
CFU/mL.
3.11.2. Shake the water sample vigorously. Flame the neck of the
bottle or sanitize the outside of sample container with 70%
Isopropyl alcohol and pour 100 mL of the water sample into the
filter funnel. Use the graduations on the filter funnel to measure
the water volume tested.
3.11.9. For total Coliforms from the filter report result as Present or
Absent In 100mL water sample.
Specifications:
4. ATTACHMENTS:
Attachment VI
MEDIA, REAGENTS, SOLUTIONS AND POSITIVE CONTROL ORGANISMS TRACKING
INFORMATION
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HISTORY OF CHANGES
:
Title
:
SIGNATURE PAGE
Dalvinder Singh
QC Senior Manager, Raw Materials QUALITY CONTROL-LA-OHM LABS 07-Jun-2016 Reviewed and Approved By
Gira Shah
QA Group Leader, Documentation QUALITY ASSURANCE-TR-OHM LABS 07-Jun-2016 Reviewed and Approved By
This document was approved and signed electronically and this is the manifestation of the
electronic signature.
GENERAL PROCEDURE
Document No. : GP000040
Version No. : 4.0; Effective
Effective Date : 14-Jun-2016
Review Due : 13-Jun-2019
Title : SOLUBILITY
Title : SOLUBILITY
Procedure:
NOTES:
1) Soluble Pharmacopeial and National Formulary articles, when brought into solution,
may show traces of physical impurities, such as minute fragments of filter paper,
fibers, and other particulate matter, unless limited or excluded by definite tests or
other specifications in the individual monographs.
2) This test is for information purposes only and is only applicable if it is part individual
Monograph.
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HISTORY OF CHANGES
:
Title
:
SIGNATURE PAGE
Dalvinder Singh
Associate Director, Quality Control QUALITY CONTROL-LA-OHM LABS 16-Aug-2017 Reviewed and Approved By
Bhupendra Patel
Senior Director, Quality Assurance QUALITY ASSURANCE-TR-OHM 17-Aug-2017 Reviewed and Approved By
LABS
This document was approved and signed electronically and this is the manifestation of the
electronic signature.
Procedure
Sieve Analysis:
In the Sieving process a weighed quantity of the powder is passed over a perforated screen,
sufficiently small particles will pass through, while those that are oversized will be retained
on the sieve. The test is performed by using a particular sieve or a set of sieves as
specified, and calculating in percentage the amount passing through or retained on the
sieve. The test is performed by using a set of USP standard sieves, mounted on a
mechanical sieve shaker which gives both gyratory and vertical tapping motions. The sieves
are arranged vertically in the order of increasing fineness with the receiver placed below the
finest mesh. Sieve analysis is performed by one of the following methods.
Procedure:
Calculation:
GENERAL PROCEDURE
Document No. : GP000039
Version No. : 4.0; Effective
Effective Date : 22-Aug-2017
Review Due : 20-Aug-2020
Title : PARTICLE SIZE (BY SIEVE ANALYSIS)
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Procedure:
Calculation:
Procedure:
NOTE:
1) The test sieves should be thoroughly cleaned after each use, using only air jet or
a liquid stream followed by drying of the sieves.
2) Sieve should be checked for gross distortions and fractures, especially at their
screen frame joints, before use.
3) For more than one sample, clean and dry the specified sieve and reuse the same
sieve.
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CC014237 GP000039 Ver. 1.0 Format revised as per the new electronic
(reference to old docDocumentum Compliance Manager (DCM) system.
series STP-030 Rev. 03)
CC094763 GP000039 Ver. 3.0 Logo / template revised from “Ranbaxy” to “Sun
Pharma” due to the merger.
:
Title
:
SIGNATURE PAGE
Dalvinder Singh
QC Senior Manager, Raw Materials QUALITY CONTROL-LA-OHM LABS 02-Jun-2016 Reviewed and Approved By
Bhupendra
Patel Site Head of Quality QUALITY ASSURANCE-TR-OHM LABS 02-Jun-2016 Reviewed and Approved By
This document was approved and signed electronically and this is the manifestation of the
electronic signature.
Method
If required, calibrate the pycnometer by filling it with recently boiled and cooled water at
25 C or specified temperature and weigh (Wc). (Assuming that the weight of 1 ml of
water at 25 C when weighed in air of density 0.0012 g/mL is 0.99602 calculate the
capacity of pycnometer).
Adjust the temperature of the substance to be examined, to about 20 C and fill the
pyconometer with it.
GENERAL PROCEDURE
Document No. : GP000028
Version No. : 4.0; Effective
Effective Date : 04-Jun-2016
Review Due : 03-Jun-2019
Title : SPECIFIC GRAVITY
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(Ws – Wt)
Specific Gravity = -----------------
(at specified temp.) (Wc – Wt)
Where:
Calibration:
The constants A and B are determined by operating the instrument with the U-tube
filled with two different samples of known density (e.g., degassed water and air).
Perform the control measurements daily, using degassed water. The results displayed
for the control measurement using degassed water do not deviate from the reference
3
value (r25 = 0.997043 g/cm ) by more than its specified error. Precision is a function of
the repeatability and stability of the oscillator frequency. Density meters are able to
–3 –5 3
achieve measurements with an error on the order of 1 × 10 g/cm3 to 1 × 10 g/cm
–4 3 –6 3
and a repeatability of 1 × 10 g/cm to 1 × 10 g/cm . For example, an instrument
–4 3 3
specified to ±1 × 10 g/cm must display 0.9970 ± 0.0001 g/cm in order to be suitable
for further measurement, otherwise a readjustment is necessary. Calibration with
certified reference materials should be carried out regularly.
Procedure:
Using the manufacturer's instructions, perform the measurements using the same
procedure as for Calibration. If necessary, equilibrate the liquid to be examined at
25°C before introduction into the tube to avoid the formation of bubbles and to reduce
the time required for measurement. Factors affecting accuracy include the following:
• temperature uniformity throughout the tube,
• nonlinearity over a range of density,
• parasitic resonant effects, and
• viscosity, if the oscillating transducer density meters used do not provide
automatic compensation of sample viscosity influence.
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:
Title
:
SIGNATURE PAGE
Dalvinder Singh
QC Senior Manager, Raw Materials QUALITY CONTROL-LA-OHM LABS 29-Jul- Reviewed and Approved By
2016
Rama Chitirala
QA Sr. Manager, Operations Oversight QUALITY ASSURANCE-TR-OHM LABS Reviewed and Approved By
29-Jul-2016
This document was approved and signed electronically and this is the manifestation of the
electronic signature.
Title : pH MEASUREMENT
Principle : The quantity pH is the logarithm (to the base 10) of the
reciprocal of the hydrogen ion concentration or is equal to the
logarithm of the hydrogen ion concentration with negative
sign. The method has the advantage that all states of acidity
and alkalinity between those of solutions containing 1 mol/L of
hydrogen ions and 1 mol/L of hydroxide ions can be
expressed by a series of positive number 0 and 14.
Apparatus
Note: The measuring system has traditionally been referred to as the “pH meter”. While the
pH meter is still in common use, the measuring system can also be embedded inside
the pH sensor, and the pH signal can be transmitted digitally to an external device
such as a computer, Programmable Logic Controller (PLC), Distributed Control
System (DCS), data acquisition system, terminal, or other microprocessor-controlled
device.
Temperature
Lab based pH measurements are typically performed at 25°C ± 2°C unless otherwise
specified in individual monograph or herein. However temperatures outside this range are
acceptable if samples are more conveniently prepared at alternative temperatures.
GENERAL PROCEDURE
Document No. : GP000026
Version No. : 8.0; Effective
Effective Date : 01-Aug-2016
Review Due : 31-Jul-2019
Title : pH MEASUREMENT
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Requirements
The instrument is calibrated against the reference buffer solutions for the purpose of
establishing a practical and operational system. The buffer solutions must be stored in
bottles of alkali free glass or plastic containers and should be protected from atmospheric
Carbon dioxide.
Table I
Potassiu
Potassiu
m Potassium Potassiu Equimol
Temperatu m Tetra-
Hydrogen Dihydrogen m al
re oxalate,
Tartrate Citrate, 0.05 Biphthala Phospha
(°C) 0.05 m
Saturated M te, te,
10 1.67 at 25°C
— — 4.00 6.92
15 1.67 — 3.80 4.00 6.90
20 1.68 — 3.79 4.00 6.88
25 1.68 3.56 3.78 4.01 6.86
30 1.68 3.55 3.77 4.02 6.85
35 1.69 3.55 3.76 4.02 6.84
40 1.69 — — 4.04 6.84
45 1.70 — — 4.05 6.83
50 1.71 — — 4.06 6.83
55 1.72 — — 4.08 6.83
60 1.72 — — 4.09 6.84
∆pH/∆C 0.0010 0.0014 0.0022 0.0018 0.0016
(Continued)
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(Continued)
Potassium
Dihydrogen Calcium
Sodiu Sodium Carbonate,
Temperatu Phosphate, 0.0087 Hydroxid
m 0.025 M, and
re M, and Disodium e,
Tetrabora Sodium
(°C) Hydrogen Saturated
te, Bicarbonate,
Phosphate, 0.0303 at 25°C
0.01 m 0.025 M
10 M
— 9.33 — 13.00
15 7.45 9.28 10.12 12.81
20 7.43 9.23 10.06 12.63
25 7.41 9.18 10.01 12.45
30 7.40 9.14 9.97 12.29
35 7.39 9.10 9.93 12.13
40 — 9.07 — 11.98
45 — 9.04 — 11.84
50 — 9.01 — 11.71
55 — 8.99 — 11.57
60 — 8.96 — 11.45
∆pH/∆C 0.0028 0.0074 0.0096 0.0310
1. Calibrate the pH meter as per the calibration procedure using buffer solutions as prepared
above. Instrument should read the pH according to the pH of buffer solution.
2. Examine the electrodes, especially the reference electrode and electrolyte level, if a liquid
electrolyte is used. If necessary, replenish electrolyte supply, and observe other
precautions indicated by the instrument and electrode manufacturers. The calibration or
verification of the pH measurement system should be periodically executed. The historical
performance of the measurement system, the criticality of the pH measurement, the
maintenance of the pH sensor, and the frequency of measurement operation is used to
determine the frequency of the calibration/verification. If the pH of the buffer is sensitive
to ambient carbon dioxide, then use Purified Water that has been recently boiled, and
subsequently stored in a container designed to minimize ingress of carbon dioxide.
2.1 To standardize the pH measurement system, select three buffer solutions for
standardization, preferably either 1.68, 4.00 & 7.00 or 4.00, 7.00 &10.01, such that
the expected pH of the material under test falls within their range. Two of the
buffers are used for the calibration process, and the third buffer is used for
verification. The value of the verification buffer should be between the calibration
buffers. If the operational range of the pH sensor is beyond the pH range of the
buffer solutions in Table 1, then either 1) select two nearby pH buffers from Table 1
or 2) select one from Table 1 and another documented prepared buffer that is
outside the range. Note: Commercially available buffer solutions of 4.01 and 10.00
may also be used.
2.2 Rinse the pH sensor several times with water, then with the first buffer solution.
2.4 Continue the 2-point calibration sequence with the second buffer according to
manufacturer's instructions.
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2.8 Continue the 2-point calibration sequence with the second buffer according to
manufacturer's instructions.
2.9 After completion of the 2-point calibration process, verify that the pH slope and
offset are within acceptable parameters. Typical acceptable parameters are slopes
ranging from 90%–105% and an offset of 0 ± 30 mV (0.5 pH units at 25°C).
Depending on the pH instrumentation, the pH slope and offset may be determined
in software or by manual methods. If using manual methods, follow supplier
instructions to calculate the pH sensor slope/offset. If these parameters are not
within acceptable parameters, the sensor should be properly cleaned, replenished,
serviced, or replaced, and the 2-point calibration process shall be repeated.
2.10 Remove the pH sensor from the second buffer, and rinse thoroughly with water,
and then the verification buffer.
2.11 Immerse the pH sensor in the verification buffer.
3. Wash the electrode with distilled / deionized water and blot dry. Immerse the electrode in
the solution under test and measure the pH at the same temperature as for the buffer
solutions.
NOTES
1. All solutions and suspensions of substances being examined and the reference buffer
solutions must be prepared in Carbon dioxide-free water.
2. Activate the new electrode by dipping it in 0.1 N Hydrochloric acid overnight and make it
free from acid by washing it with purified water thoroughly.
3. When the apparatus is used frequently, checking of the pH scale must be carried out
regularly. If the apparatus is not in frequent use, checking should be carried out before
each measurement.
PRECAUTIONS
3. Always keep the electrode properly immersed in water / buffer solution as recommended
by the electrode manufacturer.
4. If the electrode response is slow and drifting, change the electrolyte in the electrode.
HISTORY OF CHANGES
CC082206 GP000026 Ver. 7.0 Step 2.9 under procedure section revised for manual
methods statement and offset.
:
Title
:
SIGNATURE PAGE
Daniel Savad
QA Senior Documentation Associate QUALITY ASSURANCE-TR-OHM LABS 21-Apr-2016 Reviewed and Approved By
Hemendra Makwana
Senior Executive-Quality Control QC OSD - DEWAS 22-Apr-2016 Reviewed and Approved By
Dalvinder Singh
QC Senior Manager, Raw Materials QUALITY CONTROL-LA-OHM LABS 22-Apr-2016 Reviewed and Approved By
Bhupendra
Patel Site Head of Quality QUALITY ASSURANCE-TR-OHM LABS 22-Apr-2016 Reviewed and Approved By
This document was approved and signed electronically and this is the manifestation of the
electronic signature.
Procedure:
There are three methods available to determine the water content when the articles contain
water of hydration.
GENERAL PROCEDURE
Document No. : GP000025
Version No. : 4.0; Effective
Effective Date : 23-Apr-2016
Review Due : 22-Apr-2019
Title : DETERMINATION OF WATER
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Determine the water by Method Ia, unless otherwise specified in the individual monograph.
NOTE :
In case of Coulometric titration unless otherwise specified in the specification carry out the
determination of water by Method Ic – i for coulometric titration without using oven.
Principle:
In the original titrimetric solution, known as Karl Fischer Reagent, the Sulfur dioxide and
Iodine are dissolved in Pyridine and Methanol. The sample may be titrated with the
Reagent directly, or the analysis may be carried out by a residual titration procedure. The
stoichiometry of the reaction is not exact, and the reproducibility of a determination
depends upon such factors as the relative concentrations of the Reagent ingredients, the
nature of the inert solvent used to dissolve the sample and the technique used in the
particular determination. Therefore, an empirically standardized technique is used in
order to achieve the desired accuracy. Precision in the method is governed largely by the
extent to which atmospheric moisture is excluded from the system. The titration of water
is usually carried out with the use of anhydrous Methanol as the solvent for the test
specimen. In some cases, other suitable solvents may be used for special or unusual test
specimens. In these cases, the addition of at least 20% of methanol or other primary
alcohol is recommended.
Standardization of the reagent can be done by any one of the two methods.
For precise determination of significant amount of water use purified water for
standardisation.
F= W / V
Where:
For determination of trace amount of water (less than 1%) it is preferable to use
reagent with a water equivalency factor of NMT 2.0 Sodium tartarate dihydrate
may be used as a convenient water reference substance.
3. Titrate with Karl Fischer reagent to the end point potentiometrically. Calculate
the water equivalence factor F, in mg of water per mL of reagent by the
formula.
F = 0.1566 W / V
Where:
FCV/KF
Where :
Note: C is between 30% and 100% for manual titration, and between 10%
and 100% for the instrumental method endpoint determination.
1.5.2.1 Capsules:
1.5.2.2 Tablets:
1.6.2 Quickly add the samples solution, mix and again titrate with the Karl Fischer
reagent to the end-point potentiometrically.
1.7 Calculations:
V x F x 100
Water = -----------------
(%w/w) W
Where:
Principle:
In the Residual titration, excess Reagent is added to the test specimen, sufficient time is
allowed for the reaction to reach completion, and the unconsumed Reagent is titrated
with a standard solution of water in a solvent such as Methanol. The Residual titration
procedure is applicable generally and avoids the difficulties that may be encountered in
the direct titration of substances from which the bound water is released slowly.
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Calculate the water content, in mg per mL, of the water solution taken by the
formula:
VF / 25
Where:
V =
Volume of the Reagent consumed.
F =
Water equivalence factor of the
Reagent.
Determine the water content of the water solution weekly, and standardize the
Reagent against it periodically as needed.
F(XI - XR)
Where:
Notes:
1) If the sample reacts with medium then this method is not valid.
2) Use Pyridine as medium for Keto compounds.
3) This method is applicable where method mentions determination of water Ia
and Ib, otherwise refer the pharmacopoeia as per the status of the material.
Principle:
The Karl Fischer reaction is used in the coulometric determination of water. Iodine,
however, is not added in the form of a volumetric solution but is produced in an Iodide-
containing solution by anodic oxidation. The reaction cell usually consists of a large
anode compartment and a small cathode compartment that are separated by a
diaphragm. Other suitable types of reaction cells (e.g., without diaphragms) may also be
used. Each compartment has a platinum electrode that conducts current through the cell.
Iodine, which is produced at the anode electrode, immediately reacts with water present
in the compartment. When all the water has been consumed, an excess of iodine occurs,
which usually is detected electrometrically, thus indicating the endpoint. Moisture is
eliminated from the system by pre-electrolysis.
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3.1 Apparatus:
3.2 Reagents:
Where the sample is an insoluble solid, the water may be extracted using a
suitable anhydrous solvent from which an appropriate quantity, accurately
weighed, may be injected into the analyte solution. Alternatively an
evaporation technique may be used in which water is released and
evaporated by heating the sample in a tube in a stream of dry inert gas, this
gas being then passed into the cell.
3.4 Procedure:
Using a dry syringe, quickly inject the sample solution, accurately measured and
estimated to contain 0.5 to 5 mg of water, or as recommended by the instrument
manufacturer into the analyte, mix, and perform the Coulometric titration to the
electrometric endpoint. Read the water content of the sample solution directly from
the instrument's display, and calculate the percentage that is present in the sample.
Perform a blank determination, and make any necessary corrections.
THIS IS A PRINTED COPY OF AN ELECTRONIC DOCUMENT. PLEASE CHECK ITS VALIDITY
CC000111 GP000025 Ver. 1.0 Revised to bring in-line with Ranbaxy General
procedure GP000059 (old number GP015-09),
electronic system Documentum format and current
USP.
CC032458 GP000025 Ver. 2.0 Sections for principle under 1.0 (Method Ia) and
3.0 (Method Ic) revised.
CC078567 GP000025 Ver. 3.0 Logo / template revised from Ranbaxy to Sun
Pharma due to the merger.
No change to the content of the document
except version number.
:
Title
:
SIGNATURE PAGE
Jalpa Pandya
Chemist - II QC 31-Jul- Reviewed and Approved By
2018
Gira Shah
Manager, Quality Assurance QUALITY ASSURANCE-TR-OHM LABS Reviewed and Approved By
31-Jul-2018
This document was approved and signed electronically and this is the manifestation of the
electronic signature.
The terms melting range, melting point, or melting temperature are all used in
pharmacopeial contexts. Most substances exhibit a melting transition, spanning the
temperatures at which the first detectable change of phase or liquid phase is detected
to the temperature at which no solid phase is apparent. The transition may appear
instantaneous for a highly pure material, but usually a range is observed from the
beginning to the end of the process. Factors influencing this transition include the
sample size, the particle size, the efficiency of heat diffusion within the sample, and
the heating rate, among other variables, that are controlled by procedure instructions.
For pharmacopeial purposes, the temperatures of the beginning (onset temperature)
and end of transition (clear temperature) represent the melting range, except as
defined otherwise for Procedure for Class II and Procedure for Class III below. The
terms melting point and melting temperature are considered to be equivalent.
Substances which melt with no decomposition or chemical change are known to melt
congruently. In these cases, the melting point is taken to be the end of the melting
range, i.e., the temperature at which no solid phase is apparent. In some articles, the
melting process is accompanied by simultaneous decomposition, which is visually
evidenced as a side event like darkening of the material, charring, bubbling, or other
incident. These transitions are known to be non-congruent. The visual impact of this
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The signature page is the first page of the
document
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GENERAL PROCEDURE
Document No. : GP000024
Version No. : 5.0; Effective
Effective Date : 01-Aug-2018
Review Due : 30-Jul-2021
Title : MELTING RANGE OR TEMPERATURE
This document is signed electronically in Documentum-version 6.5
When no class is designated in the monograph, use the procedure for Class Ia for
crystalline or amorphous substances and the procedure for Class II for waxy
substances.
1.1 Apparatus I:
Reduce the substance under test to a very fine powder, and, unless otherwise
directed, render it anhydrous when it contains water of hydration by drying it at the
temperature specified in the monograph, or, when the substance contains no water of
hydration, dry it over a suitable desiccant for not less than 16 hours (or at the
conditions stated in Loss on Drying <731>, if appropriate).
Charge a capillary glass tube, one end of which is sealed, with a sufficient amount of
the dry powder to form a column in the bottom of the tube to a nominal height of 3 mm
high when packed down as closely as possible by moderate tapping on a solid
surface. Due to the instrument design, alternative sample sizes may be used as
instructed by the instrument manufacturer.
Operate the apparatus according to the manufacturer's instructions. Heat the block
until the temperature is about 5 degrees below the expected melting point and is rising
at a rate of about 1°/min. Insert the capillary as directed in Procedure for Class I,
Apparatus I, and continue heating until melting is complete.
The temperature at which the column of the substance under test is observed to
collapse definitely against the side of the tube at any point indicates the beginning of
melting, and the temperature at which the test substance becomes liquid throughout
corresponds to the end of melting or the melting point. The two temperatures fall
within the limits of the melting range. If melting occurs with decomposition, the melting
temperature corresponding to the beginning of the melting (melting point) is within the
range specified.
Carefully melt the material to be tested at as low a temperature as possible, and draw
it into a capillary tube, which is left open at both ends, to a depth of about 10 mm.
Cool the charged tube at 10°, or lower, for 24 hours, or in contact with ice for at least
2 hours. Then attach the tube to the thermometer by suitable means, adjust it in a
water bath so that the upper edge of the material is 10 mm below the water level.
Heat the bath until the temperature is about 5° below the expected melting point.
Continue the heating, with constant stirring, sufficiently to cause the temperature to
achieve the ramp rate of about 1.0 degrees per minute.
The temperature at which the material is observed to rise in the capillary tube is the
melting temperature.
Precautions:
Calibrate the thermometer against reference standard, that melt nearest to the melting
range of the substances to be tested.
For substances which decompose on heating note the temperature at which frothing
begins or note the temperature at which decomposition starts till the complete
decomposition occurs. Report melting with decomposition.
HISTORY OF CHANGES
:
Title
:
SIGNATURE PAGE
Dalvinder Singh
QC Senior Manager, Raw Materials QUALITY CONTROL-LA-OHM LABS 02-Jun-2016 Reviewed and Approved By
Bhupendra
Patel Site Head of Quality QUALITY ASSURANCE-TR-OHM LABS 02-Jun-2016 Reviewed and Approved By
This document was approved and signed electronically and this is the manifestation of the
electronic signature.
Method I
Apparatus
1. Weighing bottle
2. Thermostatic oven/vacuum oven (Drying chamber)
3. Desiccator/vacuum desiccators
Sample Quantity
GENERAL PROCEDURE
Document No. : GP000022
Version No. : 4.0; Effective
Effective Date : 04-Jun-2016
Review Due : 03-Jun-2019
Title : LOSS ON DRYING
Printed By : Page No: 2/7
Arti Pandya Printed Time (IST) : 09-Mar-2019 12:59 AM
This document is signed electronically in Documentum-version 6.5
Use powder as specified in the specification or monograph from not less than 4 tablets
ground to a fine powder.
c. For Capsules
Use powder as specified in the specification or monograph from a portion of the mixed
contents of not less than 4 capsules.
NOTE :
If the sample is in the form of large particle size, reduce the particle size to about 2 mm
by quickly crushing.
PROCEDURE
1. Place the weighing bottle with stopper with an identity mark under the same conditions to
be used in the determination of Loss on drying for 30 min.
2. Cool it to room temperature in a desiccator and weigh (W1). Record the weight.
3. Put the specified quantity of sample into the bottle. Replace the stopper and accurately
weigh the bottle and the contents (W2). Record the weight.
4. Distribute the sample evenly as practicable to a depth of 5 mm generally and not more
than 10 mm in case of bulky materials by gentle sidewise shaking.
5. Place the bottle in the drying chamber, remove the stopper and leave it in the drying
chamber.
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NOTE: The temperature specified in the monograph is to be regarded as being within the
range of + 2°C of the stated figure.
Desiccator
Where drying in a desiccator is specified, exercise particular care to ensure that the
desiccant is kept fully effective by frequent replacement.
The term in vacuum denotes exposure to a pressure of less than 20 mm (2.67 kPa) of
mercury unless otherwise indicated.
Calculations
W2 – W3
Loss on drying = ----------------- x 100
(%w/w) W2 – W1
Where:
a. The term constant weight means that two consecutive weights do not differ by more
than 0.5 mg/g of material, the second weighing being made after an additional hour of
drying under the specified conditions.
1. Set the drying temperature knob of IR moisture balance at 105°C or as specified in the
individual specifications or individual manufacturing instruction.
7. Note down the moisture content of sample displayed on display board of IR moisture
balance once the loss on drying over.
THIS IS A PRINTED COPY OF AN ELECTRONIC DOCUMENT. PLEASE CHECK ITS VALIDITY
2. Where drying in a desiccator is specified, exercise particular care to ensure that the
desiccant is kept fully effective by frequent replacement.
4. Use rust free clean tongs for handling the weighing bottle.
5. Ensure that the oven is clean from inside before placing the bottle inside the oven.
6. If the substance melts at a lower temperature than that specified for the determination
of Loss on drying, maintain the bottle with its contents for 1 – 2 hours at a temperature
5 - 10°C below the melting temperature, then dry at the specified temperature.
CC034442 GP000022 Version 2.0 Triennial review with no change in the content of
document.
CC079936 GP000022 Ver. 3.0 Logo / template revised from "Ranbaxy" to "Sun
Pharma" due to the merger.
Two new Precautions added.
:
Title
:
SIGNATURE PAGE
Bhaskar Reddy
Manager, Quality Assurance QUALITY CONTROL-TR-OHM LABS 03-Jan-2018 Reviewed and Approved By
Bhupendra
Patel Senior Director, Quality Assurance QUALITY ASSURANCE-TR-OHM 03-Jan-2018 Reviewed and Approved By
LABS
This document was approved and signed electronically and this is the manifestation of the
electronic signature.
Methods:
Method-I: Determine the amount of heavy metals by Method-I, unless otherwise specified.
Method-I is used for substances that yield clear, colorless preparations under the specified
test conditions.
Method-II: Method-II is used for substances that do not yield clear, colorless preparations
under the test conditions specified for Method-I, or for substances that, by virtue of their
complex nature, interfere with the precipitation of metals by sulfide ion, or for fixed and volatile
oils.
Method-III: A wet-digestion method, is used only in those cases where neither Method-I nor
Method-II can be used.
GENERAL PROCEDURE
Document No. : GP000020
Version No. : 5.0; Effective
Effective Date : 04-Jan-2018
Review Due : 02-Jan-2021
Title : HEAVY METALS
Printed By : Page No: 2/9
Arti Pandya Printed Time (IST) : 09-Mar-2019 1:31 AM
This document is signed electronically in Documentum-version 6.5
Dissolve 159.8 mg of Lead nitrate in 100 mL of water to which has been added 1 mL of Nitric
acid, then dilute with water to 1000 mL. Prepare and store this solution in glass containers
free from soluble lead salts.
Prepare on the day of use. Dilute 10.0 mL of Lead Nitrate Stock Solution with water to
100.0 mL. Each mL of Standard Lead Solution contains the equivalent of 10 µg of lead. A
comparison solution prepared on the basis of 100 µL of Standard Lead Solution per g of
substance being tested contains the equivalent of 1 part of lead per million parts of substance
being tested.
To 200 g of glycerin add water to bring the total weight to 235 g. Add 140 mL of 1 N sodium
hydroxide and 50 mL of water.
Thioacetamide TS:
Mix 0.2 mL of thioacetamide TS and 1 mL of glycerin base TS, and heat in a boiling water bath
for 20 seconds. Use the mixture immediately.
1. METHOD-I:
Test Preparation:
Into a 50-mL color-comparison tube place 25 mL of the solution prepared for the test as
directed in the individual specification; or, using the designated volume of acid where
specified in the individual specification, dissolve in and dilute with water to 25 mL the
quantity, in g, of the substance to be tested, as calculated by the formula:
2.0/(1000L)
Monitor Preparation:
Procedure:
To each of the three tubes containing the Standard Preparation, the Test Preparation,
and the Monitor Preparation, add 2 mL of pH 3.5 Acetate Buffer, then add 1.2 mL of
Thioacetamide glycerin base TS, dilute with water to 50 mL, mix, allow to stand for
£
2 minutes, and view downward over a white surface the color of the solution from the
Test Preparation is not darker than that of the solution from the Standard Preparation,
and the color of the solution from the Monitor Preparation is equal to or darker than that
of the solution from the Standard Preparation.
THIS IS A PRINTED COPY OF AN ELECTRONIC DOCUMENT. PLEASE CHECK ITS VALIDITY
2. METHOD-II:
Test Preparation:
2.0 / (1000L)
in which L is the Heavy metals limit, in percentage. Transfer the weighed quantity of
the substance to a suitable crucible, add sufficient Sulfuric acid to wet the substance,
and carefully ignite at a low temperature until thoroughly charred. (The crucible may be
loosely covered with a suitable lid during the charring.) Add to the carbonized mass
2 mL of Nitric acid and 5 drops of sulfuric acid, and heat cautiously until white fumes no
longer are evolved. Ignite, preferably in a muffle furnace, at 500°C to 600°C, until the
carbon is completely burned off. Cool, add 4 mL of 6 N Hydrochloric acid, cover, digest
on a steam bath for 15 minutes, uncover, and slowly evaporate on a steam bath to
dryness. Moisten the residue with 1 drop of Hydrochloric acid, add 10 mL of hot water,
and digest for 2 minutes. Add 6 N Ammonium hydroxide drop wise until the solution is
just alkaline to litmus paper, dilute with water to 25 mL, and adjust with 1 N Acetic acid
to a pH between 3.0 and 4.0, using short-range pH indicator paper as an external
indicator. Filter if necessary, rinse the crucible and the filter with 10 mL of water,
combine the filtrate and rinsing in a 50-mL color-comparison tube, dilute with water to
40 mL, and mix.
Procedure:
To each of the tubes containing the Standard preparation and the Test preparation, add
2 mL of pH 3.5 Acetate Buffer, then add 1.2 mL of Thioacetamide-glycerin base TS,
dilute with water to 50 mL, mix, allow to stand for 2 minutes, and view downward over a
£
white surface : the color of the solution from the Test Preparation is not darker than that
of the solution from the Standard Preparation.
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Standard Preparation:
Test Preparation:
2.0/(1000L)
For Solids:
Transfer the weighed quantity of the test substance to a clean, dry, 100 mL Kjeldahl
flask.
Cool, dilute cautiously with a few mL of water, and rinse into a 50 mL color-comparison
tube, taking care that the combined volume does not exceed 25 mL.
For Liquids:
Transfer the weighed quantity of the test substance to a clean, dry, 100-mL Kjeldahl
flask.
Clamp the flask at an angle of 45°, and cautiously add a few mL of a mixture of 8 mL of
Sulfuric acid and 10 mL of Nitric acid. Warm gently until the reaction commences, allow
the reaction to subside, and add portions of the same acid mixture, heating after each
addition, until a total of 18 mL of the acid mixture has been added. Increase the
amount of heat, and boil gently until the solution darkens. Cool, add 2 mL of Nitric acid,
and heat again until the solution darkens. Continue the heating, followed by addition of
Nitric acid until no further darkening occurs, then heat strongly to the production of
dense, white fumes. Cool, cautiously add 5 mL of water, boil gently to the production of
dense, white fumes, and continue heating until the volume is reduced to a few mL.
Cool, cautiously add 5 mL of water, and examine the color of the solution. If the color is
yellow, cautiously add 1 mL of 30 percent hydrogen peroxide, and again evaporate to
the production of dense, white fumes and a volume of 2 to 3 mL. If the solution is still
yellow, repeat the addition of 5 mL of water and the Peroxide treatment.
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Cool, dilute cautiously with a few mL of water, and rinse into a 50-mL color-comparison
tube, taking care that the combined volume does not exceed 25 mL.
Monitor Preparation:
Proceed with the digestion, using the same amount of sample and the same procedure
as directed in the subsection If the substance is a solid in the section Test Preparation,
until the step “Cool, dilute cautiously with a few mL of water.” Add 2.0 mL of Lead
Standard Solution (20 µg of lead), and mix. Transfer to a 50 mL color comparison tube,
rinse the flask with water, adding the rinsing to the tube until the volume is 25 mL, and
mix.
Procedure:
Treat the Test preparation, the Standard preparation, and the Monitor preparation as
follows. Using a pH meter or short-range pH indicator paper as external indicator,
adjust the solution to a pH between 3.0 and 4.0 with Ammonium hydroxide (a dilute
Ammonia solution may be used, if desired, as the specified range is approached), dilute
with water to 40 mL, and mix. To each tube add 2 mL of pH 3.5 Acetate Buffer, then
add 1.2 mL of Thioacetamide–glycerin base TS, dilute with water to 50 mL, mix, allow
£
to stand for 2 minutes, and view downward over a white surface : the color of the Test
Preparation is not darker than that of the Standard Preparation, and the color of the
Monitor Preparation is equal to or darker than that of the Standard Preparation.
HISTORY OF CHANGES
CC080403 GP000020 Ver. 3.0 Footnote added after view downward over a
white surface for countries where
Thioacetamide cannot be used.
Preparation for Glycerin-base TS,
Thioacetamide TS and Thioacetamide-
Glycerin TS removed.
Logo / template revised from "Ranbaxy" to
"Sun Pharma" due to the merger.
:
Title
:
SIGNATURE PAGE
Dalvinder Singh
QC Senior Manager, Raw Materials QUALITY CONTROL-LA-OHM LABS 12-Jul- Reviewed and Approved By
2016
Rama Chitirala
QA Sr. Manager, Operations Oversight QUALITY ASSURANCE-TR-OHM LABS Reviewed and Approved By
13-Jul-2016
This document was approved and signed electronically and this is the manifestation of the
electronic signature.
PROCEDIMIENTO GENERAL
Document No. : GP000018
Version No. : 4.0; EffectivO
Fecha : 14-Jul-2016
efectiva : 13-Jul-2019
Review Due :
ARSENICO
Title
Título : ARSENICO
Métodos (USP)
Disolver 132,0 mg de trióxido de arsénico, previamente secado a 105 C durante 1 hora y pesado con
precisión, en 5 mL de solución de hidróxido de sodio (1 de cada 5) en un matraz volumétrico de 1 L.
Neutralizar la solución con ácido sulfúrico 2 N, añadir 10 mL más de ácido sulfúrico 2N, luego añadir
agua recién hervida y enfriada a volumen, y mezclar.
Transfiera 10,0 mL de solución madre de trióxido de arsénico a un matraz aforado de 1000 mL, añada
10 mL de ácido sulfúrico 2 N, luego añada agua recién hervida y enfriada para completar el volumen,
y mezcle. Cada mL de Solución de Arsénico Estándar contiene el equivalente a 1 µg de Arsénico (As).
Mantenga esta solución en un recipiente de vidrio y utilícela dentro de los 3 días.
1. MÉTODO I
Pipetee 3,0 mL de Solución de Arsénico Estándar en un matraz generador, y dilúyalo con agua hasta
35 mL.
3.0 / L
en el que L es el límite de arsénico en ppm, se disuelve en agua y se diluye con agua hasta 35 mL.
1.3. Reactivos
Ácido sulfúrico (7 N)
Solución de yoduro de potasio TS (16,5 % p/v) Ácido más fuerte Solución de cloruro estanoso
Dietilditiocarbamato de plata TS
1.1. Procedure
Traten la preparación estándar y la preparación de la prueba de la siguiente manera:
2. 2. Dejar reposar a temperatura ambiente durante 30 min. 3. Llenar el tubo depurador (c)
con dos trozos de algodón que han sido empapados en una solución saturada de
acetato de plomo, liberados del exceso de solución por expresión, y secados al vacío a
temperatura ambiente, dejando un espacio de 2 mm entre los dos trozos. Lubrique las
juntas (b y d) con una grasa adecuada para la llave de paso diseñada para su uso con
disolventes orgánicos, y conecte la unidad de depuración al tubo absorbedor (e).
4. 4. Añada 3,0 g de zinc granulado (malla 20) a la mezcla del matraz, conecte
inmediatamente la unidad depuradora montada y permita que la evolución del
Hidrógeno y el desarrollo del color prosigan a temperatura ambiente durante 45 min,
agitando el matraz suavemente a intervalos de 10 min.
NOTAS:
2. Si hay presentes compuestos que contienen halógenos, utilice una temperatura más baja
mientras calienta la muestra de prueba con ácido sulfúrico, evite hervir la mezcla y añada el
peróxido de hidrógeno con precaución, antes de que comience la carbonización, para evitar la
pérdida del arsénico trivalente.
3.0/ L
Añade con precaución, gota a gota, un 30 por ciento de peróxido de hidrógeno, permitiendo que la reacción
se calme y que se caliente de nuevo entre gotas. Añada las primeras gotas muy lentamente con suficiente
mezcla, para evitar una reacción rápida. Interrumpa el calentamiento si la espuma se vuelve excesiva.
Cuando la reacción haya disminuido, calentar con precaución, girando el matraz de vez en cuando para evitar
que el espécimen se apelmace en el vidrio expuesto a la unidad de calentamiento. Mantener las condiciones
de oxidación en todo momento durante la digestión añadiendo pequeñas cantidades de la solución de
peróxido de hidrógeno siempre que la mezcla se vuelva marrón u oscura. Continúe la digestión hasta que la
materia orgánica sea destruida, elevando gradualmente la temperatura de la placa calefactora hasta que los
vapores del trióxido de azufre evolucionen copiosamente y la solución se vuelva incolora o conserve sólo un
ligero color pajizo. Enfríe, añada cautelosamente 10 ml de agua, mezcle y vuelva a evaporar hasta obtener
una fuerte humareda, repitiendo este procedimiento para eliminar cualquier rastro de peróxido de hidrógeno.
Enfríe, añada con precaución 10 mL de agua, lave los lados del matraz con unos pocos mL de agua y diluya
con agua hasta 35 mL.
2.3. Procedimiento
Los metales o las sales de metales como el cromo, el cobalto, el cobre, el mercurio, el molibdeno, el níquel, el
paladio y la plata pueden interferir en la evolución de la arsina. El Antimonio, que forma la Estibina, produce
una interferencia positiva en el desarrollo del color con el Dietilditiocarbamato de Plata TS; cuando se
sospecha la presencia de Antimonio, los colores rojos producidos en las dos soluciones de
Dietilditiocarbamato de Plata pueden ser comparados en la longitud de onda de máxima absorbencia entre
535 nm y 540 nm, con un colorímetro adecuado, ya que a esta longitud de onda la interferencia debida a la
Estibina es insignificante
HISTORIAL DE CAMBIOS
CCR Sustituye (Número y Cambio(s) realizado(s)
Número última versión)
:
Title
:
PÁGINA DE
FIRMAS
Ronak Patel
oTTROSS Asuntos 11-Jul-2016 Revisado y aprobado por
Regulatorios
Gira Shah
Líder del Grupo QA, GARANTÍA DE CALIDAD-TR-OHM 11-Jul- Revisado y aprobado por
Documentación LABS 2016
Este documento fue aprobado y firmado electrónicamente y esta es la manifestación de la firma
electrónica.
Almacenamiento : No aplicable
Embalaje : No se aplica
Nombre del fabricante: No Aplicable
PRUEBA REQUISITO
REFERENCI
A DEL
MÉTODO
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ESTA ES UNA COPIA IMPRESA DE UN DOCUMENTO ELECTRÓNICO. POR FAVOR, COMPRUEBE SU VALIDEZ ANTES D
HISTORIAL DE CAMBIOS
CCR Sustituye (Número y Cambio(s) realizado(s)
Número última versión)
:
Title
:
PÁGINA DE
FIRMAS
Ronak Patel
OTROS Asuntos 11-Jul-2016 Reviewed and Approved By
Regulatorios
El carbono orgánico total (COT) del agua puede ser medido en línea o en el
modo de muestra de agarre (modo fuera de línea).
Agua con reactivo USP / Agua MilliQ como agua con reactivo USP
2.2.2 Estándar de idoneidad del sistema:
Nota:
2.2.4 Procedimiento:
2.2.5.1 Realizar la adecuación del sistema del instrumento TOC fuera de línea una vez por
semana y/o antes de probar las muestras de agarre.
2.2.5.2 Realizar la adecuación del sistema del instrumento COT en línea una vez por
semana.
2.1.1.1 2.2.5.3 El Analizador COT en línea debe ser monitoreado por el Supervisor de
Producción diariamente.
3.2 La conductividad del agua purificada para todos los puertos de usuario debe
realizarse semanalmente una vez según la versión actual de OP000058.
3.5 Etapa 1:
Nota: Utilice un recipiente de HDPE calificado para recoger el agua para la prueba
de conductividad
3.5.3 Si la conductividad medida no es mayor que el valor de la tabla, el agua cumple los requisitos de
la prueba de conductividad. Si la conductividad es mayor que el valor de la tabla, proceda con la Etapa
2.
0 0.6
5 0.8
10 0.9
15 1.0
20 1.1
25 1.3
30 1.4
35 1.5
40 1.7
45 1.8
50 1.9
55 2.1
60 2.2
65 2.4
70 2.5
75 2.7
80 2.7
85 2.7
90 2.7
95 2.9
100 3.1
+
µS/cm (microSiemen per centimeter) = µmho/cm = reciprocal of Megohm-cm.
3.6 Etapa 2:
3.7 Etapa 3:
HISTORY OF CHANGES
:
Titulo
:
PÁGINA DE
FIRMAS
Mukul Sanghvi
Gerente Senior AR&D 04-Ene- Revisado y aprobado por
2019
Bhupendra
Patel Director Superior de Garantía de GARANTÍA DE CALIDAD-TR-OHM 04-Ene- Revisado y aprobado por
Calidad LABS 2019
Este documento fue aprobado y firmado electrónicamente y esta es la manifestación de la firma
electrónica.
Fabricante : CABOT
Reactivos:
Reactivos de grado reactivo ACS de carbonato de potasio anhidro o
agua purificada equivalente
Procedimiento:
Transfiera 5 mg de la muestra a un crisol de platino y mézclelo con
200 mg de carbonato de potasio anhidro. Caliente el crisol hasta que
adquiera un color rojo con la ayuda de un mechero Bunsen o
cualquier otra fuente de calor adecuada durante 10 minutos, y
enfríelo. Disuelva el fundido en 2 mL de agua recién destilada,
calentándolo si es necesario, y añada lentamente 2 mL de molibdato
de amonio TS a la solución. Se produce un color amarillo intenso.
Obsérvese:
No descarte la solución resultante. Guárdela para la prueba de
identificación B.
Reactivos:
O-tolidina. Reactivos de grado reactivo ACS o
equivalente
Ácido acético glacial. Reactivos de grado reactivo de ACS o
equivalente
Hidróxido de amonio. Reactivos de grado reactivo ACS o
equivalente
p r:
Impreso o Arti Pandya Tiempo de impresion
ESTA ES UNA COPIA IMPRESA DE UN DOCUMENTO ELECTRÓNICO. POR FAVOR, COMPRUEBE SU VALIDEZ AN
Procedimiento:
Precaución:
Evite el contacto con o-tolidina al realizar esta prueba, y realice la prueba en una campana bien
ventilada.
Procedimiento:
Coloque una gota de la solución amarilla de silicomolibdato obtenida en la prueba de identificación
A en un papel de filtro, y evapore el disolvente. Añada 1 gota de una solución saturada de o-
tolidina en ácido acético glacial para reducir el silicomolibdato a azul de molibdeno, y coloque el
papel sobre hidróxido de amonio. Se produce una mancha azul verdosa.
Reactivos:
Agua (Milli Q o equivalente)
Procedimiento:
Pesar con precisión alrededor de 1 g de la muestra y añadir 25 mL de agua. Agitar continuamente
para formar una dispersión uniforme. Determine el pH a 25 ± 2 °C.
Procedimiento:
Secar la muestra en un crisol de platino tarado a 105 °C durante 2 horas.
Pesar un crisol de platino que ha sido secado durante 30 minutos a 105 °C y enfriado a
temperatura ambiente en un desecador (W1).
Transfiera alrededor de 1 a 2 g de muestra en el crisol y pese con precisión el crisol con la muestra
(W2).
Mediante una suave sacudida lateral, distribuya la muestra de prueba lo más uniformemente
posible. Colocar el crisol cargado en el horno de secado. Secar la muestra a 105 ° C durante 2
horas. Al abrir la estufa, retire el crisol rápidamente y déjelo alcanzar la temperatura ambiente en un
desecador antes de pesarla. (W3)
Nota: Retenga la muestra seca en el crisol para que se pierda en la prueba de ignición. Cálculo:
Determine la pérdida por secado utilizando la siguiente fórmula.
W2 - W3
% Pérdida del secado =
W2 - W1 x 100
Dónde,
W1 = Peso del crisol de platino vacío
W2 = Peso del crisol de platino y de la muestra antes del secado.
W3 = Peso del crisol de platino y de la muestra después del
secado
Calculos:
% Pérdida de la W2 Wn
ignición = W2
100
W1
Dónde,
W1 = Wt. del crisol vacío de la prueba de pérdida en el secado.
W2 = Wt. de la muestra con el crisol antes de la ignición por la prueba de pérdida por secado
Wn = Wt. de la muestra y el crisol después de los encendidos a peso constante (n = 3, 4, 5,...)
Contratado a un laboratorio externo para hacer pruebas o realizarlas internamente como sigue:
Preparación estándar:
Pipetear 3 mL de Solución de Arsénico Estándar en un matraz generador, y diluir con agua hasta 35 mL.
Preparación de la prueba:
Transferir 2,5 g a un matraz, añadir 50 mL de ácido clorhídrico 3 N y refluir durante 30 minutos utilizando un
condensador de agua. Enfríe, filtre con la ayuda de la succión, y transfiera el filtrado a un
Un matraz volumétrico de 100 ml. Lave el filtro y el matraz con varias porciones de agua
caliente, y añadir los lavados al frasco. Enfríe, diluya con agua hasta el volumen y mezcle:
una porción de 15.0- mL de esta solución, a la que se han añadido 3 mL de ácido
clorhídrico, cumple con los requisitos de la prueba. Se omite la adición de ácido sulfúrico
7N..
Procedimiento:
Trate la preparación estándar y la preparación para la prueba de manera similar como se indica a
continuación. Añada 2 mL de yoduro de potasio TS, 0.5 mL de cloruro de estaño de ácido más
fuerte TS, y 1 mL de alcohol isopropílico, y mezcle. Deje reposar a temperatura ambiente durante
30 minutos. Empaquetar el tubo depurador con dos trozos de algodón empapados en una solución
saturada de acetato de plomo, liberados del exceso de solución por expresión, y secados al vacío a
temperatura ambiente, dejando un espacio de 2 mm entre los dos trozos. Lubrique las uniones con
una grasa adecuada para la llave de paso diseñada para su uso con disolventes orgánicos, y
conecte la unidad del depurador al tubo absorbedor. Transfiera 3.0 mL de dietilditiocarbamato de
plata TS al tubo absorbedor. Añada 3,0 g de zinc granulado (malla 20) a la mezcla del matraz,
conecte inmediatamente la unidad depuradora ensamblada y permita que la evolución del
hidrógeno y el desarrollo del color prosiga a temperatura ambiente durante 45 minutos, agitando el
matraz suavemente a intervalos de 10 minutos. Desconecte el tubo absorbedor de las unidades
generadora y depuradora, y transfiera la solución absorbente a una celda de absorción de 1 cm.
Cualquier color rojo producido por la Preparación de la Prueba no excede el producido por la
Preparación Estándar. Si es necesario o deseable, determine la absorbencia a la longitud de onda
de máxima absorbencia entre 535 y 540 nm, con un espectrofotómetro o colorímetro adecuado,
utilizando el dietilditiocarbamato de plata TS como blanco..
Equipo:
Horno de mufla
Balance analítico
Temporizador
Reactivos:
Ácido sulfúrico. Reactivos de grado reactivo ACS o equivalente
Ácido fluorhídrico. Reactivos de grado reactivo ACS o equivalente
El alcohol. Reactivos de grado reactivo de ACS o
equivalente
Pag No: 7/10
Impreso por Arti Pandya Tiempo de impression 13-Mar-2019 3:43 AM
(IST) :
Este documento está firmado electrónicamente en Documentum-versión 6. 5
ESTA ES UNA COPIA IMPRESA DE UN DOCUMENTO ELECTRÓNICO. POR FAVOR, COMPRUEBE SU VALIDEZ ANTES D
Procedimiento:
Pesar un crisol de platino, previamente encendido a 1000 ± 25 °C durante 30 minutos y enfriado a
temperatura ambiente en un desecador (W1). Transfiera con precisión unos 500 mg de la muestra a un
crisol de platino y registre el peso combinado de la muestra y el crisol (W2). Enciéndalo a 1000 ± 25 °C
durante 2 horas, enfríelo en un desecador y péselo (W3). Añadir 3 gotas de ácido sulfúrico, y añadir
suficiente alcohol para humedecer completamente la muestra. Añadir 15 mL de ácido fluorhídrico, y en una
campana bien ventilada evaporar en una placa caliente hasta la sequedad, usando calor medio (95 °C a
105 °C) y teniendo cuidado de que la muestra no se salpique al acercarse a la sequedad. Caliente el crisol
hasta que adquiera un color rojo con la ayuda de un quemador Bunsen. Encienda el residuo a 1000 ± 25
°C durante 30 minutos, enfríe en un desecador y pese (W4). Si queda un residuo, repita el procedimiento,
comenzando por "añadir 15 ml de ácido fluorhídrico". El peso perdido por la muestra, previamente
encendido a 1000 ± 25 °C, representa el peso de SiO2 en la porción tomada.
Calculo:
% VALORACION = (W3 - W1) - (W4 - W1)
(W3 - W1)
100
Dónde,
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