Accessed from 10.6.1.

1 by merck1 on Mon May 11 21:21:16 EDT 2015

2092 Alfuzosin / Official Monographs USP 38

System suitability solution: 0.03 mg/mL of USP Al- N-Formyl analog: N-[3-[(4-Amino-6,7-dimethoxy-
fuzosin System Suitability Mixture A RS in Diluent from quinazolin-2-yl)(methyl)amino]propyl]formamide.
the System suitability stock solution C15H21N5O3 319.36
Standard stock solution: 0.15 mg/mL of USP Alfuzosin
Hydrochloride RS in methanol
Standard solution: 0.03 mg/mL of USP Alfuzosin Hy-
drochloride RS in Diluent from the Standard stock .

solution Allantoin
System suitability
Samples: System suitability solution and Standard
solution
Suitability requirements
Resolution: NLT 1.0 between alfuzosin and the
furamide analog, and NLT 1.0 between deacylated al-
fuzosin and the N-formyl analog, System suitability C4H6N4O3 158.12
solution Urea, (2,5-dioxo-4-imidazolidinyl)-;
Relative standard deviation: NMT 2.0%, Standard Allantoin [97-59-6].
solution
Analysis DEFINITION
Samples: Standard solution and Sample solution Allantoin contains NLT 98.5% and NMT 101.0% of
Calculate the percentage of each impurity in the por- C4H6N4O3.
tion of Tablets taken:
IDENTIFICATION
Result = (rU/rS) × (CS/CU) × 100 • A. INFRARED ABSORPTION 〈197K〉
• B. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST
rU = peak response for each impurity from the 〈201〉: The RF value of the principal spot from Sample
Sample solution solution B corresponds to that from Standard solution A,
rS = peak response for alfuzosin from the Sample as described in the test for Organic Impurities.
solution
CS = concentration of USP Alfuzosin Hydrochloride ASSAY
RS in the Standard solution (mg/mL) • PROCEDURE
CU = nominal concentration of alfuzosin Sample: 120 mg
hydrochloride in the Sample solution Analysis: Transfer the Sample to a 100-mL beaker, dis-
(mg/mL) solve by stirring in 40 mL of water, and titrate with 0.1
Acceptance criteria: See Table 7. M sodium hydroxide. Use a suitable electrode system
(see Titrimetry 〈541〉). Each mL of 0.1 M sodium hy-
droxide is equivalent to 15.81 mg of C4H6N4O3.
Table 7 Acceptance criteria: 98.5%–101.0%
USP Monographs

Relative Acceptance
Retention Criteria, IMPURITIES
Name Time NMT (%) • RESIDUE ON IGNITION 〈281〉: NMT 0.1%
• ORGANIC IMPURITIES
Deacylated alfuzosina 0.46 0.40
.

Adsorbent: Cellulose
N-Formyl analogb . 0.50 0.30 Diluent: Methanol and water (1:1)
Alfuzosin 1.0 — Urea stock solution: 1 mg/mL of USP Urea RS in water
Furamide analogc . 1.18 —d .
Standard solution A: 1 mg/mL of USP Allantoin RS in
Any individual unspecified Diluent
— Standard solution B: 0.1 mg/mL of USP Urea RS in
impurity 0.20
Total impurities — 0.80 methanol, from Urea stock solution
Standard solution C: Standard solution A and Standard
a N2-(3-Aminopropyl)-6,7-dimethoxy-N2-methylquinazoline-2,4-diamine.
. . .

solution B (1:1)
b N-[3-[(4-Amino-6,7-dimethoxyquinazolin-2-yl)(methyl)ami-
.

no]propyl]formamide. Sample solution A: Transfer 0.10 g of Allantoin to a

c N-[3-[(4-Amino-6,7-dimethoxyquinazolin-2-yl)(methyl)ami- 10-mL volumetric flask, add 5 mL of water, dissolve by
heating, and allow to cool. Dilute with methanol to vol-
.

no]propyl]furan-2-carboxamide.
d Furamide analog, a component of USP Alfuzosin System Suitability Mix-
.
ume. [NOTE—Use immediately after preparation.]
ture A RS, is not a specified impurity. Sample solution B: Transfer 1 mL of Sample solution A
ADDITIONAL REQUIREMENTS to a 10-mL volumetric flask, and dilute with Diluent to
• PACKAGING AND STORAGE: Protect from light and mois- volume.
ture. Store at controlled room temperature. Spray reagent: 5 mg/mL of p-dimethylaminobenzalde-
• LABELING: When more than one Dissolution test is given, hyde in a mixture of methanol and hydrochloric acid
the labeling states the Dissolution test used only if Test 1 (3:1)
is not used. Application volume
• USP REFERENCE STANDARDS 〈11〉 Standard solution A: 5 µL
USP Alfuzosin Hydrochloride RS Standard solution B: 5 µL
USP Alfuzosin System Suitability Mixture A RS Standard solution C: 5 µL
Furamide analog: N-{3-[(4-Amino-6,7-dimethoxy- Sample solution A: 10 µL
quinazolin-2-yl)(methyl)amino]propyl}furan- Sample solution B: 5 µL
2-carboxamide. Developing solvent system: Butyl alcohol, glacial ace-
C19H23N5O4 385.42 tic acid, and water (60:15:25)
Deacylated alfuzosin: N2-(3-Aminopropyl)-6,7- Analysis: Proceed as directed for Chromatography 〈621〉,
Thin-Layer Chromatography. Develop the chromatogram
.

dimethoxy-N2-methylquinazoline-2,4-diamine.
until the solvent front has moved about 10 cm. Spray
.

C14H21N5O2 291.35
the plate with Spray reagent, dry in a current of hot air,
and after 30 min examine under visible light.

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 21:21:16 EDT 2015

USP 38 Official Monographs / Allopurinol 2093

Acceptance criteria: Any spot from Sample solution A, Related compounds—[NOTE—Store and inject the Stan-
except for the principal spot, is not more intense than dard solution and the Test solution at 8°, using a cooled
the spot from Standard solution B (NMT 0.5%). The test autosampler.]
is not valid unless the principal spots from Standard so- Solution A—Dissolve 1.25 g of monobasic potassium
lution C are clearly separated. phosphate in 1000 mL of water, filter, and degas.
SPECIFIC TESTS Solution B—Use methanol.
• ACIDITY OR ALKALINITY Mobile phase—Use variable mixtures of Solution A and So-
Sample solution: 5 mg/mL in carbon dioxide-free water lution B as directed for Chromatographic system. Make ad-
Analysis: To 5 mL of the Sample solution add 5 mL of justments if necessary (see System Suitability under Chroma-
water, 0.1 mL of methyl red TS, and 0.2 mL of 0.01 M tography 〈621〉).
sodium hydroxide. Diluent—Prepare a mixture of Solution A and Solution B
Acceptance criteria: A yellow color is observed. The (90:10).
solution turns red upon the addition of 0.4 mL of 0.01 Allopurinol related compound F solution—Accurately weigh
M hydrochloric acid. about 5 mg of USP Allopurinol Related Compound F RS into
• LOSS ON DRYING 〈731〉: Dry a sample at 105° to constant a suitable flask. Add 2.0 mL of 0.1 N sodium hydroxide,
weight: it loses NMT 0.1% of its weight. promptly sonicate with swirling for 1 to 3 minutes to dis-
• REDUCING SUBSTANCES solve, add 80 mL of Diluent, and sonicate for an additional
Sample solution: 1.0 g of Allantoin in 10 mL of water. 5 minutes.
Shake for 2 min, and filter.
Analysis: To the Sample solution add 1.5 mL of 0.02 M Standard stock solution—Accurately weigh about 5 mg
potassium permanganate. each of USP Allopurinol RS, USP Allopurinol Related Com-
Acceptance criteria: The solution remains violet for at pound A RS, USP Allopurinol Related Compound B RS, USP
least 10 min. Allopurinol Related Compound C RS, USP Allopurinol Re-
lated Compound D RS, and USP Allopurinol Related Com-
ADDITIONAL REQUIREMENTS pound E RS, and transfer to a 100-mL volumetric flask. Add
• USP REFERENCE STANDARDS 〈11〉 2.0 mL of 0.1 N sodium hydroxide, promptly sonicate with
USP Allantoin RS swirling for not more than 1 minute to dissolve, add the
USP Urea RS entire volume of Allopurinol related compound F solution to
the flask, rinse the flask in which Allopurinol related com-
pound F solution was prepared with a small amount of Dilu-
ent, and add the rinsings to the solution. Sonicate for an
additional 5 minutes. Dilute with Diluent to volume. [NOTE—
This solution is stable for 48 hours when stored at 8°.]
Allopurinol
.

Standard solution—Quantitatively dilute an accurately

measured volume of the Standard stock solution with Diluent
to obtain a solution having known concentrations of about
0.5 µg of allopurinol and about 0.5 µg each of allopurinol

USP Monographs
related compounds A, B C, D, E, and F per mL.
Test solution—Transfer about 25 mg of Allopurinol, accu-
C5H4N4O 136.11 rately weighed, to a 100-mL volumetric flask, add 5.0 mL of
4H-Pyrazolo[3,4-d]pyrimidin-4-one, 1,5-dihydro-. 0.1 N sodium hydroxide to dissolve, promptly sonicate with
1,5-Dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one. swirling for not more than 1 minute, add 80 mL of Diluent,
1H-Pyrazolo[3,4-d]pyrimidin-4-ol [315-30-0]. and sonicate for an additional 5 minutes. Dilute with Diluent
to volume.
» Allopurinol contains not less than 98.0 percent Chromatographic system (see Chromatography 〈621〉)—The
and not more than 102.0 percent of C5H4N4O, liquid chromatograph is equipped with a 220-nm detector
and a 4.6-mm × 25-cm column that contains 5-µm packing
calculated on the dried basis. L1. The column temperature is maintained at 30°. The flow
Packaging and storage—Preserve in well-closed contain- rate is about 1.0 mL per minute. The chromatograph is pro-
ers. Store at room temperature. grammed as follows.
USP Reference standards 〈11〉—
USP Allopurinol RS Time Solution A Solution B
USP Allopurinol Related Compound A RS (minutes) (%) (%) Elution
3-Amino-4-carboxamidopyrazole hemisulfate. 0–30 90→70 10→30 linear gradient
(C4H6N4O)2 · H2SO4 350.32 30–35 70 30 isocratic
USP Allopurinol Related Compound B RS 35–36 70→90 30→10 linear gradient
5-(Formylamino)-1H-pyrazole-4-carboxamide. 36–46 90 10 re-equilibration
C5H6N4O2 154.13
USP Allopurinol Related Compound C RS Chromatograph the Standard solution, identify the peaks
N-(4H-1,2,4-Triazol-4-yl)-1H-pyrazole-4-carboxamide. (see Table 1), and record the peak responses as directed for
C6H6N6O 178.15 Procedure: the resolution, R, between allopurinol related
USP Allopurinol Related Compound D RS compounds C and B is not less than 0.8; and the tailing
Ethyl 5-amino-1H-pyrazole-4-carboxylate. factor for the allopurinol peak is not more than 1.5.
C6H9N3O2 155.15 Procedure—Separately inject equal volumes (about 40 µL)
USP Allopurinol Related Compound E RS of the Standard solution and the Test solution into the chro-
Ethyl 5-(formylamino)-1H-pyrazole-4-carboxylate. matograph, record the chromatograms, and identify the al-
USP Allopurinol Related Compound F RS lopurinol peak and the peaks due to impurities listed in Ta-
Ethyl 3-(2-carbethoxy-2-cyanoethenyl)amino-1H- ble 1.
pyrazole-4-carboxylate.
Identification, Infrared Absorption 〈197K〉.
Loss on drying 〈731〉—Dry it in vacuum at 105° for
5 hours: it loses not more than 0.5% of its weight.

Official from May 1, 2015

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