Abacavir Oral Solution
DEFINITION
Abacavir Oral Solution contains 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
Solution A:
Trifluoroacetic acid and water (0.05:99.95)
Solution B:
Methanol and water (17:3)
Diluent:
1 mL of phosphoric acid diluted with water to 1000 mL
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 | 0 | 100 |
| 50 | 0 | 100 |
| 51 | 95 | 5 |
| 55 | 95 | 5 |
System suitability solution:
0.2 mg/mL of USP Abacavir System Suitability Mixture RS in Diluent
Standard solution:
0.46 mg/mL of USP Abacavir Sulfate RS in Diluent
Sample solution:
Equivalent to 0.4 mg/mL of abacavir in Diluent, from Oral Solution. [Note—Sonicate, if necessary. ]
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
3.9-mm × 15-cm; 5-µm packing L1
Column temperature:
30
Flow rate:
0.8 mL/min
Injection size:
10 µL
System suitability
Samples:
System suitability solution and Standard 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 Oral Solution taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak area of abacavir from the Sample solution |
| rS | = | = peak area 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) |
| Mr1 | = | = molecular weight of abacavir mutiplied by 2, 572.66 |
| Mr2 | = | = molecular weight of abacavir sulfate, 670.74 |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Deliverable Volume 
698
:
Meets the requirements
698:
Meets the requirements
IMPURITIES
Organic Impurities
• Procedure
Solution A, Solution B, Diluent, Mobile phase, System suitability solution, Standard solution, Sample solution, Chromatographic system, and System suitability:
Proceed as directed in the Assay.
Sensitivity solution:
0.2 µg/mL of USP Abacavir Sulfate RS in Diluent, from the Standard solution. [Note—The concentration of this solution is 0.05% of the nominal concentration of the Sample solution. ]
Analysis
Samples:
Diluent, Standard solution, Sample solution, and Sensitivity solution. [Note—In the Sample solution disregard any peaks corresponding to peaks identified in the Diluent and any peak with a peak area less than the abacavir peak area in the Sensitivity solution. ]
Calculate the percentage of each impurity in the portion of Oral Solution taken:
Result = (rU/rS) × (CS/CU) × (1/F) × (Mr1/Mr2) × 100
| rU | = | = peak area of abacavir from the Sample solution |
| rS | = | = peak area 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 from Impurity Table 1 |
| Mr1 | = | = molecular weight of abacavir mutiplied by 2, 572.66 |
| Mr2 | = | = molecular weight of abacavir sulfate, 670.74 |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 2.0%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Cyclopropyldiaminopurine abacavira | 0.57 | 1.4 | 0.3 |
| Descyclopropyl abacavirb | 0.68 | 1.0 | 0.8 |
| Abacavir | 1.00 | — | — |
| trans-Abacavirc | 1.04 | 1.0 | — |
| Any individual unspecified 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. It is a process impurity and monitored in the drug substance.
|
|||
SPECIFIC TESTS
• Microbial Enumeration Tests 61 and Tests For Specified Microorganisms 62:
The total aerobic microbial count does not exceed 100 cfu/mL, and the total combined molds and yeast count does not exceed 10 cfu/mL. It also meets the requirement for absence of Escherichia coli.
61 and Tests For Specified Microorganisms 62:
The total aerobic microbial count does not exceed 100 cfu/mL, and the total combined molds and yeast count does not exceed 10 cfu/mL. It also meets the requirement for absence of Escherichia coli.
• pH 791:
3.8–4.5
791:
3.8–4.5
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers. Store at controlled room temperature.
• USP Reference Standards 11
11
USP Abacavir Sulfate RS 
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USP Abacavir System Suitability Mixture RS
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A mixture containing 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 |
| 61 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 62 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2022
Pharmacopeial Forum: Volume No. 36(3) Page 652