Abacavir Tablets
DEFINITION
Abacavir Tablets contain Abacavir Sulfate equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of abacavir (C14H18N6O).
IDENTIFICATION
• 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
Diluent:
1.0 mL of phosphoric acid in 1 L of water
Solution A:
Trifluoroacetic acid and water (0.05:99.95)
Solution B:
Methanol and water (85:15)
Mobile phase:
See the gradient table below.
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 95 | 5 |
| 20 | 70 | 30 |
| 35 | 10 | 90 |
| 40 | 10 | 90 |
| 41 | 95 | 5 |
| 50 | 95 | 5 |
System suitability solution:
0.2 mg/mL of USP Abacavir System Suitability Mixture RS in Diluent
Standard solution:
0.21 mg/mL of abacavir sulfate in Diluent (equivalent to 0.18 mg/mL of abacavir), from USP Abacavir Sulfate RS
Sample stock solution:
Transfer the equivalent to 1500 mg of abacavir, from a portion of Tablets, into a 250-mL volumetric flask. Add 150 mL of Diluent. Shake mechanically for 45 min. Dilute with Diluent to volume. Pass a portion through a suitable filter of 0.45-µm or finer pore size. Discard the first 3 mL of the filtrate.
Sample solution:
0.18 mg/mL of abacavir in Diluent using the filtrate obtained in the Sample stock solution
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
3.9-mm × 15-cm; packing L1
Flow rate:
0.8 mL/min
Injection size:
10 µL
System suitability
Samples:
Standard solution and System suitability solution
Suitability requirements
Resolution:
NLT 1.5 between abacavir and trans-abacavir, 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 Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response of abacavir from the Sample solution |
| rS | = | = peak response of abacavir from the Standard solution |
| CS | = | = concentration of abacavir sulfate in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of abacavir in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of abacavir multiplied by 2, 572.66 |
| Mr2 | = | = molecular weight of abacavir sulfate, 670.74 |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Medium:
0.1 N hydrochloric acid; 900 mL
Apparatus 2:
75 rpm
Time:
15 min
Standard solution:
0.39 mg/mL of USP Abacavir Sulfate RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Spectrometric conditions
Mode:
UV absorption spectroscopy
Analytical wavelength:
254 nm
Blank:
Medium
Calculate the percentage of abacavir dissolved:
Result = (AU/AS) × (CS/L) × (Mr1/Mr2) × V × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| Mr1 | = | = molecular weight of abacavir multiplied by 2, 572.66 |
| Mr2 | = | = molecular weight of abacavir sulfate, 670.74 |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of abacavir is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Diluent, Solution A, Solution B, Mobile phase, System suitability solution, Standard solution, Sample solution, and Chromatographic system:
Proceed as directed in the Assay.
Analysis:
[Note—Record the chromatograms for 2.5 times the retention time of abacavir. ]
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × (Mr1/Mr2) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of abacavir from the Standard solution |
| CS | = | = concentration of USP Abacavir Sulfate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of abacavir in the Sample solution (mg/mL) |
| F | = | = relative response factor for each impurity (see Impurity Table 1) |
| Mr1 | = | = molecular weight of abacavir multiplied by 2, 572.66 |
| Mr2 | = | = molecular weight of abacavir sulfate, 670.74 |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 1.0%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Cyclopropyldiaminopurine abacavira |
0.57 | 1.4 | 0.2 |
| Descyclopropyl abacavirb | 0.68 | 1.0 | 0.2 |
| Abacavir | 1.0 | — | — |
| trans-Abacavirc,d | 1.04 | — | — |
| Any other individual impurity | — | 1.0 | 0.2 |
|
a
N6-Cyclopropyl-9H-purine-2,6-diamine.
b
[(1S,4R)-4-(2,6-Diamino-9H-purin-9-yl)-cyclopent-2-enyl]methanol.
c
{(1R,4R)-4-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]-cyclopent-2-enyl}methanol.
d
Process impurity monitored in the drug substance.
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers. Store at room temperature.
• USP Reference Standards 11
11
USP Abacavir Sulfate RS 
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USP Abacavir System Suitability Mixture RS — A mixture of abacavir sulfate and trans-abacavir.
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— A mixture of abacavir sulfate and trans-abacavir.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Behnam Davani, Ph.D., M.B.A.
Senior Scientific Liaison 1-301-816-8394 |
(SM12010) Monographs - Small Molecules 1 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2023
Pharmacopeial Forum: Volume No. 36(3) Page 654