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2086 Alfentanil / Official Monographs USP 38

rT = sum of all the peak responses rU = peak response from the Sample solution
Acceptance criteria rS = peak response from the Standard solution
Any single impurity: NMT 0.5% CS = concentration of USP Alfentanil Hydrochloride
Total impurities: NMT 1.0% RS in the Standard solution (mg/mL)
CU = nominal concentration of alfentanil in the
SPECIFIC TESTS Sample solution (mg/mL)
• WATER DETERMINATION, Method I 〈921〉: NMT 4.0% Mr1 = molecular weight of alfentanil, 416.52
Mr2 = molecular weight of alfentanil hydrochloride,
ADDITIONAL REQUIREMENTS 452.98
• PACKAGING AND STORAGE: Preserve in tight containers, Acceptance criteria: 90.0%–110.0%
and store at controlled room temperature.
• USP REFERENCE STANDARDS 〈11〉 IMPURITIES
USP Alfentanil Hydrochloride RS • ORGANIC IMPURITIES
Mobile phase: Acetonitrile and 0.01 M tetrabutylam-
monium hydrogen sulfate (14:86)
Standard solution: 0.54 mg/mL of USP Alfentanil Hy-
.

drochloride RS in saline TS
Alfentanil Injection Sample solution: Equivalent to 0.50 mg/mL of al-
fentanil from a suitable volume of Injection in saline TS
DEFINITION Chromatographic system
Alfentanil Injection is a sterile solution of Alfentanil Hydro- (See Chromatography 〈621〉, System Suitability.)
chloride in Water for Injection. It contains an amount of Mode: LC
Alfentanil Hydrochloride equivalent to NLT 90.0% and Detector: UV 235 nm
NMT 110.0% of the labeled amount of alfentanil Column: 4.6-mm × 25-cm; 5-µm packing L1
(C21H32N6O3). Flow rate: 2 mL/min
[CAUTION—Handle Alfentanil Injection with great care be- Injection volume: 25 µL
cause it is a potent opioid analgesic.] System suitability
Sample: Standard solution
IDENTIFICATION Suitability requirements
• A. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST Column efficiency: NLT 5400 theoretical plates
〈201〉 Tailing factor: NMT 1.3
Standard solution: 0.54 mg/mL of USP Alfentanil Hy- Relative standard deviation: NMT 1.0%
drochloride RS Analysis
Sample solution: 0.5 mg/mL of alfentanil in water Sample: Sample solution
Chromatographic system Calculate the percentage of each impurity in the por-
Application volume: 200 µL tion of Injection taken:
Developing solvent system: Chloroform, methanol,
and formic acid (85:10:5) Result = (rU/rT) × 100
USP Monographs

Visualizing agent: Dragendorff’s reagent

Analysis rU = peak response of each impurity
Samples: Standard solution and Sample solution rT = sum of all of the peaks
Proceed as directed in the chapter. Acceptance criteria: The sum of all impurities is NMT
Acceptance criteria: Meets the requirements 2.0%.
• B. The retention time of the major peak of the Sample
solution corresponds to that of the Standard solution, as SPECIFIC TESTS
obtained in the Assay. • PH 〈791〉: 4.0–6.0
• PARTICULATE MATTER IN INJECTIONS 〈788〉: Meets the re-
ASSAY quirements for small-volume injections
• PROCEDURE • BACTERIAL ENDOTOXINS TEST 〈85〉: NMT 10 USP Endotoxin
Mobile phase: Acetonitrile and 0.01 M tetrabutylam- Units/mL
monium hydrogen sulfate (14:86) • OTHER REQUIREMENTS: Meets the requirements in Injec-
Standard solution: 0.54 mg/mL of USP Alfentanil Hy- tions 〈1〉
drochloride RS in saline TS
Sample solution: Equivalent to 0.50 mg/mL of al- ADDITIONAL REQUIREMENTS
fentanil from a suitable volume of Injection in saline TS • PACKAGING AND STORAGE: Preserve in tight, single-dose or
Chromatographic system multiple-dose containers, preferably of Type I glass, and
(See Chromatography 〈621〉, System Suitability.) store at controlled room temperature.
Mode: LC • USP REFERENCE STANDARDS 〈11〉
Detector: UV 235 nm USP Alfentanil Hydrochloride RS
Column: 4.6-mm × 25-cm; 5-µm packing L1 USP Endotoxin RS
Flow rate: 2 mL/min
Injection volume: 25 µL
System suitability
Sample: Standard solution .

Suitability requirements Alfuzosin Hydrochloride

Column efficiency: NLT 5400 theoretical plates
Tailing factor: NMT 1.3
Relative standard deviation: NMT 1.0%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of alfentanil (C21H32N6O3) in
the portion of Injection taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100 C19H27N5O4 · HCl 425.91

Official from May 1, 2015

Copyright (c) 2015 The United States Pharmacopeial Convention. All rights reserved.
Accessed from 10.6.1.1 by merck1 on Mon May 11 21:20:25 EDT 2015

USP 38 Official Monographs / Alfuzosin 2087

2-Furancarboxamide, N-[3-[(4-amino-6,7-dimethoxy- Mobile phase: Acetonitrile, tetrahydrofuran, and Buffer

2-quinazolinyl)methylamino]propyl]tetrahydro-, monohy- (20:1:80)
drochloride (±); System suitability solution: 0.4 mg/mL of USP Al-
(±)-N-[3-[(4-Amino-6,7-dimethoxy-2-quinazolinyl)methylami- fuzosin System Suitability Mixture RS in Mobile phase
no]propyl]tetrahydro-2-furamide monohydrochloride Sample solution: 0.40 mg/mL of Alfuzosin Hydrochlo-
[81403-68-1]. ride in Mobile phase
Reference solution: 0.40 µg/mL of Alfuzosin Hydro-
DEFINITION chloride in Mobile phase from the Sample solution
Alfuzosin Hydrochloride contains NLT 98.0% and NMT Chromatographic system
102.0% of alfuzosin hydrochloride (C19H27N5O4 · HCl), cal- (See Chromatography 〈621〉, System Suitability.)
culated on the anhydrous and solvent-free basis. Mode: LC
Detector: UV 254 nm
IDENTIFICATION Column: 4.6-mm × 15-cm; 5-µm packing L1
• A. INFRARED ABSORPTION 〈197K〉 Flow rate: 1.5 mL/min
• B. IDENTIFICATION TESTS—GENERAL, Chloride 〈191〉: Meets Injection volume: 10 µL
the requirements System suitability
• C. The retention time of the Sample solution corresponds Sample: System suitability solution
to that of the Standard solution, as obtained in the Assay. Suitability requirements
ASSAY Peak-to-valley ratio: The ratio of the height of the
• PROCEDURE furamide analog peak to the height of the valley be-
[NOTE—Use low-actinic glassware.] tween the furamide analog peak and alfuzosin is NLT
Solution A: 2 M sodium hydroxide 5.
Solution B: 5.0 mL of perchloric acid in 900 mL of Analysis
water. Adjust with Solution A to a pH of 3.5, and dilute Samples: Sample solution and Reference solution
with water to 1000 mL. Calculate the percentage of each impurity in the por-
Mobile phase: Acetonitrile and Solution B (30:70) tion of Alfuzosin Hydrochloride taken:
Diluent: Methanol and Solution A (500:3)
Standard stock solution: 0.5 mg/mL of USP Alfuzosin Result = (rU/rS) × (1/D) × 100
Hydrochloride RS in Diluent rU = peak response of each impurity from the
Standard solution: 0.04 mg/mL of USP Alfuzosin Hy- Sample solution
drochloride RS in Mobile phase from the Standard stock rS = peak response of alfuzosin from the Reference
solution; the solution is stable for 14 h at 5°. solution
Sample stock solution: 0.5 mg/mL of Alfuzosin Hydro- D = dilution factor between the Sample solution
chloride in Diluent and the Reference solution, 1000
Sample solution: 0.04 mg/mL of Alfuzosin Hydrochlo- Acceptance criteria: See Table 1. [NOTE—Disregard any
ride in Mobile phase from the Sample stock solution; the peak with an area less than 0.05%.]
solution is stable for 14 h at 5°.

USP Monographs
Chromatographic system
(See Chromatography 〈621〉, System Suitability.) Table 1
Mode: LC Relative Acceptance
Detector: UV 254 nm Retention Criteria,
Column: 4.6-mm × 25-cm; 5-µm packing L1 Name Time NMT (%)
Column temperature: 30° Deacylated
Autosampler temperature: 5° alfuzosina 0.5 0.20
Flow rate: 1.5 mL/min
.

Alfuzosin 1.0 —
Injection volume: 10 µL
System suitability Furamide analogb . 1.2 —c.

Sample: Standard solution Any other individual, un-

—
Suitability requirements identified impurity 0.10
Relative standard deviation: NMT 1.0% Total impurities — 0.30
Tailing factor: NMT 1.5 a N2-(3-Aminopropyl)-6,7-dimethoxy-N2-methylquinazoline-2,4-diamine.
Analysis
. . .

b N-{3-[(4-Amino-6,7-dimethoxyquinazolin-2-yl)(methyl)ami-
Samples: Standard solution and Sample solution
.

no]propyl}furan-2-carboxamide.
Calculate the percentage of alfuzosin hydrochloride c Furamide analog, a component of USP Alfuzosin System Suitability Mix-
.

(C19H27N5O4 · HCl) in the portion of Alfuzosin Hydro- ture RS, is not a specified impurity.
chloride taken:
SPECIFIC TESTS
Result = (rU/rS) × (CS/CU) × 100 • OPTICAL ROTATION 〈781〉
Sample solution: 20 mg/mL in carbon dioxide-free
rU = peak response from the Sample solution water
rS = peak response from the Standard solution Acceptance criteria: −0.10° to +0.10°
CS = concentration of USP Alfuzosin Hydrochloride • WATER DETERMINATION, Method I 〈921〉: NMT 2.0%
RS in the Standard solution (mg/mL) • PH 〈791〉
CU = concentration of Alfuzosin Hydrochloride in Sample solution: 20 mg/mL in carbon dioxide-free
the Sample solution (mg/mL) water
Acceptance criteria: 98.0%–102.0% on the anhydrous Acceptance criteria: 4.0–5.5
and solvent-free basis
ADDITIONAL REQUIREMENTS
IMPURITIES • PACKAGING AND STORAGE: Preserve in tight containers.
• RESIDUE ON IGNITION 〈281〉: NMT 0.1% Protect from light and humidity, and store at room
• ORGANIC IMPURITIES temperature.
Buffer: Dilute 5 mL of perchloric acid in 900 mL of
water. Adjust with 2 M sodium hydroxide to a pH of
3.5, and dilute with water to 1 L.

Official from May 1, 2015

Copyright (c) 2015 The United States Pharmacopeial Convention. All rights reserved.
 Accessed from 10.6.1.1 by merck1 on Mon May 11 21:20:25 EDT 2015

2088 Alfuzosin / Official Monographs USP 38

• USP REFERENCE STANDARDS 〈11〉 Chromatographic system

USP Alfuzosin Hydrochloride RS (See Chromatography 〈621〉, System Suitability.)
USP Alfuzosin System Suitability Mixture RS Mode: LC
Alfuzosin Hydrochloride containing approximately 0.4% Detector: UV 254 nm
furamide analog (N-{3-[(4-amino-6,7-dimethoxy- Column: 4.6-mm × 15-cm; 5-µm packing L1
quinazolin-2-yl)(methyl)amino]propyl}furan-2-carbox- Flow rate: 1.5 mL/min
amide), and about 0.4% deacylated alfuzosin (N2- . Injection volume: 20 µL
(3-aminopropyl)-6,7-dimethoxy-N2-methylquinazoline-
. System suitability
2,4-diamine). Sample: Standard solution
Suitability requirements
Tailing factor: 0.8–1.5 for alfuzosin
Relative standard deviation: NMT 2.0%
.

Alfuzosin Hydrochloride Extended-
Release Tablets
DEFINITION
Alfuzosin Hydrochloride Extended-Release Tablets contain
NLT 90.0% and NMT 110.0% of the labeled amount of
alfuzosin hydrochloride (C19H27N5O4 · HCl).
IDENTIFICATION
• A. INFRARED ABSORPTION 〈197〉 [NOTE—Methods described
in Infrared Absorption 〈197K〉 or 〈197A〉 may be used.]
Sample: Grind 4 Tablets, and add 20 mL of water.
[NOTE—When analyzing multi-layer Tablets, isolate the
layer containing alfuzosin hydrochloride using a suitable
tool.] Add 20 mL of strong ammonia solution. Extract
with 20 mL of methylene chloride, and separate the or-
ganic layer. Repeat the extraction successively with
20 mL, then with 10 mL of methylene chloride. Wash
the combined organic layers with 20 mL of water. Dry
the organic solution using a phase separation filter.
Take 2.0 mL of the dried organic solution, and mix with
200 mg of finely ground potassium bromide. Evaporate
the methylene chloride at 60°, then at 105° for 30 min.
Make a disk. Alternatively, evaporate methylene chloride
USP Monographs
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of alfuzosin hydrochloride
(C19H27N5O4 · HCl) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak response from the Sample solution
rS = peak response from the Standard solution
CS = concentration of USP Alfuzosin Hydrochloride
RS in the Standard solution (mg/mL)
CU = nominal concentration of the Sample solution
(mg/mL)
Acceptance criteria: 90.0%–110.0%
PERFORMANCE TESTS
• DISSOLUTION 〈711〉
Test 1
Medium: 0.01 N hydrochloric acid; 500 mL
Apparatus 2: 100 rpm, with Tablet holder (see Figure
1)

from the dried organic solution at 60°, then at 105° for

30 min. Perform the IR spectrum.
Acceptance criteria: The maxima of the spectrum ob-
tained from the Sample correspond in position and rela-
tive intensity to those obtained from USP Alfuzosin Hy-
drochloride RS, treated in the same manner as the
Sample, beginning with “add 20 mL of water.”
• B. The retention time of the major peak of the Sample
solution corresponds to that of the Standard solution, as
obtained in the Assay.
ASSAY
• PROCEDURE
Solution A: 5.0 mL of perchloric acid in 900 mL of
water. Adjust with 2 M sodium hydroxide to a pH of
3.5, and dilute with water to 1000 mL. Figure 1. 37.5-mm (l) × 20-mm (d) stainless steel cylinders
Mobile phase: Acetonitrile, tetrahydrofuran, and Solu- are used as sample holders. The cylinders contain screw
tion A (20:1:80) caps drilled with seven 4.5-mm holes. Seven 4.5-mm holes
Diluent: 0.01 N hydrochloric acid are drilled in the bottom, and 12 longitudinal series of five
Standard stock solution: 0.15 mg/mL of USP Alfuzosin 5-mm holes are drilled on the cylinders, alternatively start-
Hydrochloride RS in methanol ing and ending with one 1.7-mm hole.
Standard solution: 0.03 mg/mL of USP Alfuzosin Hy-
drochloride RS in Diluent from the Standard stock Times: 1, 6, 12, and 20 h
solution Sample solution: Pass a portion of the solution under
Sample stock solution: Place a suitable number of Tab- test through a suitable filter.
lets into a suitable volumetric flask to obtain a solution Standard solution: (L/500) mg/mL of USP Alfuzosin
having a concentration of 0.16 mg/mL of alfuzosin hy- Hydrochloride RS in Medium, where L is the Tablet la-
drochloride. Add 80% of the flask volume of methanol, bel claim in mg
and stir for at least 1 h using a magnetic stirrer. Add Detector: UV 330 nm
10% of the flask volume of Diluent, mix, and allow it to Blank: Medium
cool to room temperature. Dilute the resulting suspen- Path length: 1 cm
sion with methanol to volume, stir, and allow to settle Tolerances: See Table 1.
for 30 min.
Sample solution: 0.03 mg/mL of alfuzosin hydrochlo-
ride in Diluent from the Sample stock solution superna-
tant. Pass through a suitable filter.

Official from May 1, 2015

Copyright (c) 2015 The United States Pharmacopeial Convention. All rights reserved.