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Modernization of chapter: p

<191> Identification Tests - General


Status
<191> Identification Tests General:
Tests that are frequently referred to in the Pharmacopeia
for identification of official articles
Referenced hundreds of times in USP, NF, FCC and
DSC Monographs
Wet chemistr or flame tests Wet chemistry or flame tests
Using of potentially hazardous substances
Most tests have several reactions for the same ion
Some tests need adjustments of amounts and
concentrations concentrations
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<191> Identification Tests - General
Flame Tests: A chemical is
introduced to a flame and
K
+
Na
+
introduced to a flame and
the color imparted on the
flame is used to identify the
presence of the chemical
Color based Precipitation
Cu
+
Li
+
(Sully, 2009)
Color based Precipitation
Reactions: A designated
procedure is followed and a
positive result is denoted by
the formation of a specific
color solid or precipitate color solid or precipitate
1:20 Decanted Ammonium
Sulfate
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Disadvantages of Current Methods
Wet Chemistry Methods can be subjective and
unclear:
Dependent on telling the difference between colors
Dependent on determining the presence or absence
of precipitates
Water Penicillin G
Blank Potassium
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Background
Since last cycle 2005-2010, the former GC EC decided to
update (modernize) IDtests in <191> containing: update (modernize) ID tests in <191> containing:
Out-of-date technology
Personal safety risks Personal safety risks
Environmental concerns
Two ID tests were updated after their verification in USP labs
(official in USP 32-NF 27, S1):
Acetate
Ammonium
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Background
6
Background
Other six additional ID tests were evaluated:
Potassium
Sodium
Calcium Calcium
Zinc
Hypophosphite
Chlorate
Four projects were conducted in USP labs based Four projects were conducted in USP labs based
on EP procedures (cations)
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Background
8
Background
In October 2010, during the first CA EC face-to-face meeting,
it was concluded that further analysis should be done by the it was concluded that further analysis should be done by the
Subcommittee F (Wet Chemistry) with inclusion of Experts
from FCC and DSC:
Nancy Lewen (Chair) CA EC
Anthony Bevilacqua CA EC
Geoff Carr CA EC
J onathan DeVries FCC
Pei Chen DSC Pei Chen DSC
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Main Points for Revision
Rationale for replacement of current wet chemistry methods
Convenience of having two wet chemistry tests
A single default ID test, when applicable
Suitability for dosage forms
A way to identify different tests for the same
molecule/ion/functional group molecule/ion/functional group
Standardization of the wording, and a new style to be aligned
with the monograph redesign process
A plan on how USP will update monographs referencing these
tests, as well as how USP will incorporate the tests into new
monographs monographs
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Overview of the Process of Modernization
44 ID tests in GC <191>
19 h d
Analysis of
GC <191> tests
Analysis of
monographs
Analysis of
literature
19 use hazardous
reagents
5 flame tests
monographs
literature
Leading World
Pharmacopeias
Another approaches
8 ions were chosen
Sodium
Potassium
C l i
Chloride
S lf
f
pp
Calcium
Magnesium
Aluminum
Sulfate
Phosphate
Proposals for
modernization
Survey for
manufacturers
What manufactures
Covered about
80 % monographs
Analysis of
lab reports
Potassium
really do with ID?
Approval by EC
Sodium
Calcium
Zinc
Approval by EC
Stimuli article
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Analysis of GC <191> Tests
44 ID tests in GC <191>
19 h d
Analysis of
GC <191> tests
Analysis of
monographs
Analysis of
literature
19 use hazardous
reagents
5 flame tests
monographs
literature
Leading World
Pharmacopeias
Another approaches
8 ions were chosen
Sodium
Potassium
C l i
Chloride
S lf
2 Chlorine evolved
f
pp
Calcium
Magnesium
Aluminum
Sulfate
Phosphate
35
40
45
Lanthanum nitrate TS
Ammonium sulfide TS
Chlorine TS
Proposals for
modernization
Survey for
manufacturers
What manufactures
Covered about
80 % monographs
20
25
30
2
Mercuric chloride TS
Mercurous nitrate TS
Formaldehyde TS
Lead acetate TS
Analysis of
lab reports
Potassium
really do with ID?
Approve by EC
10
15
20 2
Potassium
permanganate TS
Potassium chromate
Hydrogen sulfide
Sodium
Calcium
Zinc
Approve by EC
Stimuli article
0
5
44 19 5
y g
Phosphine
Chloroform
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IDtests for Na+ion
Analysis of Literature
44 ID tests in GC <191>
19 h d
Analysis of
GH <191> tests
Analysis of
monographs
Analysis of
literature
80
90
100
ID tests for Na+ ion
19 use hazardous
reagents
5 flame tests
monographs
literature
Leading World
Pharmacopeias
Another approaches
8 ions were chosen
Sodium
Potassium
C l i
Chloride
S lf
30
40
50
60
70
f
pp
Calcium
Magnesium
Aluminum
Sulfate
Phosphate
0
10
20
1 2 substances Dosage forms
Proposals for
modernization
Survey for
manufacturers
What manufactures
Covered about
80 % monographs
- monographs containing ID
tests according GC <191>
- monographs containing
f l h fl
ID tests for K+ ion
25
30
Analysis of
lab reports
Potassium
really do with ID?
Approve by EC
reference only to the flame test
- monographs containing no
ID tests for target ion
- monographs which do
10
15
20
25
Sodium
Calcium
Zinc
Approve by EC
Stimuli article
have wet chemistry ID test for
target ion but do not have
rference to the GC <191>
Dosage forms
0
5
10
substances
13
f Proposals for
modernization
Survey for
manufacturers
What manufactures
really do with ID?
Approve by EC Approve by EC
Stimuli article
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Identification Testing Methods Survey Some Findings
Approximately 400 responses:
92% use wet chemistry for ID testing
64% also use additional testing methods
35% Atomic Absorption
30% Spectrophotometric methods
22% Ion Chromatography
19% Inductively Coupled Plasma
68% provided suggestions to improve or modernize the
chapter (e g addition of modern techniques or clarifying chapter (e.g. addition of modern techniques or clarifying
procedures)
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Identification Testing Methods Survey Some Findings
Top reason for favoring wet chemistry replacement was Top reason for favoring wet chemistry replacement was
that alternative methods are more quantitative and less
subjective
Top reason for being opposed was instrument cost
Nearly 20% indicated that other methods should be
alternative or optional
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Proposals for Modernization
Exclude flame tests fromIDmethods for cations
Analysis of
literature
Exclude flame tests from ID methods for cations
Replace procedures using potentially hazardous reagents
When appropriate, harmonize wet chemistry methods for ions
literature
pp p , y
When appropriate, include instrumental approaches
Evaluate the inclusion of alternative ID tests
f
Clarify the current techniques and standardize the text
Make a decision about
Proposals for
modernization
necessity ID tests for
counter ions in DF
C d t l b t di t k
Analysis of
lab reports
Approved by EC
Conduct lab studies to make
sure that proposed methods
will work properly Approved by EC
Stimuli article
will work properly
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Alternative Approaches
Evaluate ID Testing Methods Survey results auate est g et ods Su ey esuts
Perform individual revisions
Harmonize with other major pharmacopeias Harmonize with other major pharmacopeias
Evaluate instrumental approaches (Ion Chromatography,
Capillary Electrophoresis, ICPMS, Atomic Absorption, p y p , , p ,
etc.)
Publish a Stimuli Article
Others?
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USP Expert Panel
USP has established an Expert Panel (EP) to work on Modernization
of Identification Tests
Charter The purpose of this EP will be to perform a comprehensive
and holistic analysis of the current identification tests for ions and
functional groups comprised in general chapter <191> Identification g p p g p
Tests General, especially to the already identified points in need of
revision, in order to make recommendations of a suitable process of
modernization to the CA EC
Proposals of modernization could include alternative approaches
including, but not limited to: performing individual revisions of ID
tests, harmonization with other pharmacopeias, and evaluation of tests, harmonization with other pharmacopeias, and evaluation of
instrumental approaches (such as atomic absorption,
spectrophotometric methods, ion chromatography, induced coupled
plasma, etc.) p )
SM Experts and staff will work closely because of the high impact in
monographs
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Panel Members
Nancy Lewen CA EC (Chair)
Anthony Bevilacqua CA EC
G ff P R C CAEC Geoffrey P.R. Carr CA EC
J onathan DeVries FCC
Pei Chen DSC Pei Chen DSC
Bernard Olsen SM3
MichelleAdamson Michelle Adamson
Maryna Dmitriieva
Michael Hornig
J eff Rohrer SM1
Anne Warner
FDA Liaisons (TBD)
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Current Status
Expert Panel reports to Chemical Analysis Expert
Committee
Timothy J. Wozniak, Chair
Antonio Hernandez-Cardoso, Senior Scientific Liaison General Chapters
Elena Gonikberg, Principal Scientific Liaison Small Molecules
Leonel Santos, Senior Scientific Liaison Small Molecules
Kristie Laurvick, Scientific Liaison Food Chemical Codex
Huy Dinh, Scientific Liaison Dietary Supplements Compendium
Good mix of members representing key stakeholders
First face-to-face meeting scheduled by mid-J uly, 2012
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