Accessed from 10.6.1.

1 by merck1 on Thu Jun 02 19:47:55 EDT 2016

USP 39 Official Monographs / Abacavir 2281

Official Monographs for

USP 39
. 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, 2016

Copyright (c) 2016 The United States Pharmacopeial Convention. All rights reserved.
 Accessed from 10.6.1.1 by merck1 on Thu Jun 02 19:47:55 EDT 2016

2282 Abacavir / Official Monographs USP 39

Impurity Table 1 Standard solution: 0.21 mg/mL of abacavir sulfate in

Relative Relative Acceptance
Diluent (equivalent to 0.18 mg/mL of abacavir), from
Retention Response Criteria,
USP Abacavir Sulfate RS
Name Time Factor NMT (%)
Sample stock solution: Transfer the equivalent to
1500 mg of abacavir, from a portion of Tablets, into a
Cyclopropyldiami- 250-mL volumetric flask. Add 150 mL of Diluent. Shake
nopurine abacavira . 0.57 1.4 0.3 mechanically for 45 min. Dilute with Diluent to volume.
Descyclopropyl aba- Pass a portion through a suitable filter of 0.45-µm or
cavirb . 0.68 1.0 0.8 finer pore size. Discard the first 3 mL of the filtrate.
Abacavir 1.00 — — Sample solution: 0.18 mg/mL of abacavir in Diluent us-
trans-Abacavirc 1.04 1.0 — ing the filtrate obtained in the Sample stock solution
Chromatographic system
.

Any individual un-

specified impurity — 1.0 0.2 (See Chromatography 〈621〉, System Suitability.)
a N6-Cyclopropyl-9H-purine-2,6-diamine.
Mode: LC
Detector: UV 254 nm
. .

b [(1S,4R)-4-(2,6-Diamino-9H-purin-9-yl)cyclopent-2-enyl]methanol.
Column: 3.9-mm × 15-cm; packing L1
.

c {(1R,4R)-4-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]-cyclopent-2-
Flow rate: 0.8 mL/min
.

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

stance. Injection volume: 10 µL
System suitability
SPECIFIC TESTS Samples: System suitability solution and Standard
• MICROBIAL ENUMERATION TESTS 〈61〉 and TESTS FOR SPECI- solution
FIED MICROORGANISMS 〈62〉: The total aerobic microbial Suitability requirements
count does not exceed 100 cfu/mL, and the total com- Resolution: NLT 1.5 between abacavir and trans-aba-
bined molds and yeast count does not exceed 10 cfu/ cavir, System suitability solution
mL. It also meets the requirement for absence of Escher- Relative standard deviation: NMT 2.0%, Standard
ichia coli. solution
• PH 〈791〉: 3.8–4.5 Analysis
Samples: Standard solution and Sample solution
ADDITIONAL REQUIREMENTS Calculate the percentage of the labeled amount of
• PACKAGING AND STORAGE: Preserve in well-closed contain- abacavir (C14H18N6O) in the portion of Tablets taken:
ers. Store at controlled room temperature.
• USP REFERENCE STANDARDS 〈11〉 Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
USP Abacavir Sulfate RS
USP Abacavir System Suitability Mixture RS rU = peak response of abacavir from the Sample
A mixture containing abacavir sulfate and trans-abacavir solution
rS = peak response of abacavir from the Standard
solution
CS = concentration of abacavir sulfate in the
USP Monographs

Standard solution (mg/mL)

Abacavir Tablets CU = nominal concentration of abacavir in the
Sample solution (mg/mL)
DEFINITION Mr1 = molecular weight of abacavir multiplied by 2,
Abacavir Tablets contain Abacavir Sulfate equivalent to NLT 572.66
90.0% and NMT 110.0% of the labeled amount of aba- Mr2 = molecular weight of abacavir sulfate, 670.74
cavir (C14H18N6O). Acceptance criteria: 90.0%–110.0%
IDENTIFICATION PERFORMANCE TESTS
• A. The retention time of the major peak of the Sample • DISSOLUTION 〈711〉
solution corresponds to that of the Standard solution, as Medium: 0.1 N hydrochloric acid; 900 mL
obtained in the Assay. Apparatus 2: 75 rpm
Time: 15 min
ASSAY Standard solution: 0.39 mg/mL of USP Abacavir Sulfate
• PROCEDURE RS in Medium
Diluent: 1.0 mL of phosphoric acid in 1 L of water Sample solution: Pass a portion of the solution under
Solution A: Trifluoroacetic acid and water (0.05: 99.95) test through a suitable filter of 0.45-µm pore size.
Solution B: Methanol and water (85:15) Instrumental conditions
Mobile phase: See Table 1. Mode: UV
Analytical wavelength: 254 nm
Table 1 Blank: Medium
Calculate the percentage of the labeled amount of
Time Solution A Solution B abacavir (C14H18N6O) dissolved:
(min) (%) (%)
0 95 5 Result = (AU/AS) × (CS/L) × (Mr1/Mr2) × V × 100
20 70 30
35 10 90
AU = absorbance of the Sample solution
AS = absorbance of the Standard solution
40 10 90 CS = concentration of the Standard solution
41 95 5 (mg/mL)
50 95 5 L = label claim (mg/Tablet)
Mr1 = molecular weight of abacavir multiplied by 2,
System suitability solution: 0.2 mg/mL of USP Aba- 572.66
cavir System Suitability Mixture RS in Diluent Mr2 = molecular weight of abacavir sulfate, 670.74
V = volume of Medium, 900 mL
Tolerances: NLT 80% (Q) of the labeled amount of
abacavir (C14H18N6O) is dissolved.

Official from May 1, 2016

Copyright (c) 2016 The United States Pharmacopeial Convention. All rights reserved.