Accessed from 10.6.1.

1 by merck1 on Mon May 11 20:33:06 EDT 2015

USP 38 Official Monographs / Abacavir 1995

Official Monographs for

USP 38
. rU = peak area of abacavir from the Sample solution
Abacavir Oral Solution rS = peak area of abacavir from the Standard
solution
DEFINITION CS = concentration of USP Abacavir Sulfate RS in
Abacavir Oral Solution contains NLT 90.0% and NMT the Standard solution (mg/mL)
110.0% of the labeled amount of abacavir (C14H18N6O). CU = nominal concentration of abacavir in the
Sample solution (mg/mL)
IDENTIFICATION Mr1 = molecular weight of abacavir mutiplied by 2,
• The retention time of the major peak of the Sample solu- 572.66
tion corresponds to that of the Standard solution, as ob- Mr2 = molecular weight of abacavir sulfate, 670.74
tained in the Assay. Acceptance criteria: 90.0%–110.0%
ASSAY PERFORMANCE TESTS
• PROCEDURE • DELIVERABLE VOLUME 〈698〉: Meets the requirements
Solution A: Trifluoroacetic acid and water (0.05:99.95)
Solution B: Methanol and water (17:3) IMPURITIES
Diluent: 1 mL of phosphoric acid diluted with water to Organic Impurities
1000 mL • PROCEDURE
Mobile phase: See the gradient table below. Solution A, Solution B, Diluent, Mobile phase, System
suitability solution, Standard solution, Sample solu-
tion, Chromatographic system, and System suitabil-
Time Solution A Solution B ity: Proceed as directed in the Assay.
(min) (%) (%) Sensitivity solution: 0.2 µg/mL of USP Abacavir Sulfate
0 95 5 RS in Diluent, from the Standard solution. [NOTE—The
20 70 30 concentration of this solution is 0.05% of the nominal
35 10 90 concentration of the Sample solution.]

USP Monographs
40 10 90
Analysis
Samples: Diluent, Standard solution, Sample solution,
41 0 100 and Sensitivity solution. [NOTE—In the Sample solution
50 0 100 disregard any peaks corresponding to peaks identified
51 95 5 in the Diluent and any peak with a peak area less
55 95 5 than the abacavir peak area in the Sensitivity solution.]
Calculate the percentage of each impurity in the por-
System suitability solution: 0.2 mg/mL of USP Aba- tion of Oral Solution taken:
cavir System Suitability Mixture RS in Diluent
Standard solution: 0.46 mg/mL of USP Abacavir Sul- Result = (rU/rS) × (CS/CU) × (1/F) × (Mr1/Mr2) × 100
fate RS in Diluent
Sample solution: Equivalent to 0.4 mg/mL of abacavir rU = peak area of abacavir from the Sample solution
in Diluent, from Oral Solution. [NOTE—Sonicate, if rS = peak area of abacavir from the Standard
necessary.] solution
Chromatographic system CS = concentration of USP Abacavir Sulfate RS in
(See Chromatography 〈621〉, System Suitability.) the Standard solution (mg/mL)
Mode: LC CU = nominal concentration of abacavir in the
Detector: UV 254 nm Sample solution (mg/mL)
Column: 3.9-mm × 15-cm; 5-µm packing L1 F = relative response factor for each impurity from
Column temperature: 30° Impurity Table 1
Flow rate: 0.8 mL/min Mr1 = molecular weight of abacavir mutiplied by 2,
Injection size: 10 µL 572.66
System suitability Mr2 = molecular weight of abacavir sulfate, 670.74
Samples: System suitability solution and Standard Acceptance criteria
solution Individual impurities: See Impurity Table 1.
Suitability requirements Total impurities: NMT 2.0%
Resolution: NLT 1.5 between abacavir and trans-aba-
cavir, System suitability solution
Relative standard deviation: NMT 2.0%, Standard
solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of C14H18N6O in the portion of
Oral Solution taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100

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 20:33:06 EDT 2015

1996 Abacavir / Official Monographs USP 38

Impurity Table 1 Standard solution: 0.04 mg/mL of USP Abacavir Sulfate

Relative Relative Acceptance
RS in water
Retention Response Criteria,
Sample solution: 0.04 mg/mL of Abacavir Sulfate in
Name Time Factor NMT (%)
water
Chromatographic system
Cyclopropyldiami- (See Chromatography 〈621〉, System Suitability.)
nopurine abacavira . 0.57 1.4 0.3 Mode: LC
Descyclopropyl aba- Detector: UV 254 nm
cavirb . 0.68 1.0 0.8 Column: 4.6-mm × 5-cm; 5-µm packing L1
Abacavir 1.00 — — Column temperature: 30°
trans-Abacavirc 1.04 1.0 — Flow rate: 1 mL/min
Injection size: 20 µL
.

Any individual un-

specified impurity — 1.0 0.2 System suitability
a N6-Cyclopropyl-9H-purine-2,6-diamine.
Sample: Standard solution
Suitability requirements
. .

b [(1S,4R)-4-(2,6-Diamino-9H-purin-9-yl)cyclopent-2-enyl]methanol.
Relative standard deviation: NMT 1.5%
.

c {(1R,4R)-4-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]-cyclopent-2-
Analysis
.

enyl}methanol. It is a process impurity and monitored in the drug sub-

stance. Samples: Standard solution and Sample solution
Calculate the percentage of (C14H18N6O)2 · H2SO4 in the
SPECIFIC TESTS portion of Abacavir Sulfate taken:
• MICROBIAL ENUMERATION TESTS 〈61〉 and TESTS FOR SPECI-
FIED MICROORGANISMS 〈62〉: The total aerobic microbial Result = (rU/rS) × (CS/CU) × 100
count does not exceed 100 cfu/mL, and the total com-
bined molds and yeast count does not exceed 10 cfu/ rU = peak area of abacavir from the Sample solution
mL. It also meets the requirement for absence of Escher- rS = peak area of abacavir from the Standard
ichia coli. solution
• PH 〈791〉: 3.8–4.5 CS = concentration of USP Abacavir Sulfate RS in
the Standard solution (mg/mL)
ADDITIONAL REQUIREMENTS CU = concentration of Abacavir Sulfate in the
• PACKAGING AND STORAGE: Preserve in well-closed contain- Sample solution (mg/mL)
ers. Store at controlled room temperature. Acceptance criteria: 97.0%–102.0% on the anhydrous
• USP REFERENCE STANDARDS 〈11〉 and solvent-free basis
USP Abacavir Sulfate RS
USP Abacavir System Suitability Mixture RS IMPURITIES
A mixture containing abacavir sulfate and trans-abacavir Inorganic Impurities
• RESIDUE ON IGNITION 〈281〉: NMT 0.2%
Organic Impurities
• PROCEDURE 1: RELATED COMPOUNDS
USP Monographs

Solution A: Trifluoroacetic acid and water (0.05:99.95)

Abacavir Sulfate Solution B: Methanol and water (17:3)
Mobile phase: See the gradient table below.

Time Solution A Solution B

(min) (%) (%)
0 95 5
20 70 30
35 10 90
(C14H18N6O)2 · H2SO4 670.74 35.1 95 5
2-Cyclopentene-1-methanol, 4-[2-amino-6-(cyclopropyl- 50 95 5
amino)-9H-purin-9-yl]-, (1S-cis)-, sulfate (salt) (2:1);
(1S,4R)-4-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]- System suitability solution: 0.25 mg/mL of USP Aba-
2-cyclopentene-1-methanol sulfate (salt) (2:1) cavir Related Compounds Mixture RS in water
[188062-50-2]. Sample solution: 0.25 mg/mL of Abacavir Sulfate in
water
DEFINITION Chromatographic system
Abacavir Sulfate contains NLT 97.0% and NMT 102.0% of (See Chromatography 〈621〉, System Suitability.)
(C14H18N6O)2 · H2SO4, calculated on the anhydrous and Mode: LC
solvent-free basis. Detector: UV 254 nm
IDENTIFICATION Column: 3.9-mm × 15-cm; 5-µm packing L1
• A. INFRARED ABSORPTION 〈197K〉 Column temperature: 30°
• B. The retention time of the major peak of the Sample Flow rate: 1 mL/min
solution corresponds to that of the System suitability solu- Injection size: 20 µL
tion, obtained as directed in the test for Organic Impuri- System suitability
ties, Procedure 2. Sample: System suitability solution
• C. IDENTIFICATION TESTS—GENERAL, Sulfate 〈191〉 Suitability requirements
Sample solution: 5 mg/mL Resolution: NLT 1.5 between abacavir and trans-
abacavir
ASSAY Analysis
• PROCEDURE Sample: Sample solution
Mobile phase: Acetonitrile, phosphoric acid, and water Calculate the percentage of each impurity in the por-
(20:1:180) tion of Abacavir Sulfate taken:
Result = (rU/rT) × 100

Official from May 1, 2015

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