Abacavir Sulfate

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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(C₁₄H₁₈N₆O₂) · H₂SO₄      670.74

2-Cyclopentene-1-methanol, 4-[2-amino-6-(cyclopropyl amino)-9H-purin-9-yl]-, (1S-cis)-, sulfate (salt) (2:1);

(1S,4R)-4-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol sulfate (salt) (2:1) CAS RN®: 188062-50-2; UNII: J220T4J9Q2.

1 DEFINITION

Abacavir Sulfate contains NLT 97.0% and NMT 102.0% of (C H N O) · H SO , calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION

2.1 Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

B. The retention time of the major peak of the Sample solution corresponds to that of the System suitability solution, obtained as directed in the test for Organic Impurities, Procedure 2.

C. Identification Tests—General, Sulfate 〈191〉

2.2 Sample solution: 5 mg/mL

3 ASSAY

3.1 Procedure

Mobile phase: Acetonitrile, phosphoric acid, and water (20:1:180)

Standard solution: 0.04 mg/mL of USP Abacavir Sulfate RS in water

Sample solution: 0.04 mg/mL of Abacavir Sulfate in water

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 5-cm; 5-μm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection size: 20 μL

3.2 System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 1.5%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of (C₁₄H₁₈N₆O₂) · H₂SO₄ in the portion of Abacavir Sulfate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak area of abacavir from the Sample solution

r_S = peak area of abacavir from the Standard solution

C_S = concentration of USP Abacavir Sulfate RS in the Standard solution (mg/mL)

C_U = concentration of Abacavir Sulfate in the Sample solution (mg/mL)

Acceptance criteria: 97.0%–102.0% on the anhydrous and solvent-free basis

4 IMPURITIES

4.1 Inorganic Impurities

Residue on Ignition 〈281〉: NMT 0.2%

4.2 Organic Impurities

4.2.1 Procedure 1: Related Compounds

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

Solution B: Methanol and water (17:3)

Mobile phase: See the gradient table below.

System suitability solution: 0.25 mg/mL of USP Abacavir Related Compounds Mixture RS in water

Sample solution: 0.25 mg/mL of Abacavir Sulfate in water

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm × 15-cm; 5-μm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection size: 20 μL

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 1.5 between abacavir and trans-abacavir

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Abacavir Sulfate taken:

Result = (r_U/r_T) × 100

r_U = peak area of each impurity from the Sample solution

r_T = sum of the areas of all the peaks from the Sample solution

Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: NMT 0.8%

Impurity Table 1

^a [(1S,4R)-4-(2,6-Diamino-9H-purin-9-yl)cyclopent-2-enyl]methanol.

^b {(1R,4R)-4-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]-cyclopent-2-enyl}methanol.

^c N⁶-Cyclopropyl-9-{(1R,4S)-4-[(2,5-diamino-6-chloropyrimidin-4-yloxy)methyl]cyclopent-2-enyl}-9H-purine-2,6-diamine.

^d 9-[(1R,4S)-4-(tert-Butoxymethyl)cyclopent-2-enyl]-N⁶-cyclopropyl-9H-purine-2,6-diamine.

4.2.2 Procedure 2: Enantiomeric Purity

Solution A: Heptane, 2-propanol, and diethylamine (850:150:1).

Solution B: Heptane and 2-propanol (1:1)

Mobile phase: See the gradient table below.

Diluent: Methanol and triuoroacetic acid (200:1)

System suitability solution: Transfer a quantity of USP Abacavir Stereoisomers Mixture RS to a suitable volumetric ask, add a volume of

Diluent equivalent to 30% of the nal volume, and sonicate until the solid is fully dissolved. Add a volume of 2-propanol equivalent to about 30% of the nal volume, mix, and dilute with heptane to volume to obtain 0.4 mg/mL of USP Abacavir Stereoisomers Mixture RS.

Sample solution: Transfer 4 mg of Abacavir Sulfate to a 10-mL volumetric ask. Add 3 mL of Diluent, and sonicate until the solid is fully dissolved. Add 3 mL of 2-propanol, mix, and dilute with heptane to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 286 nm

Column: 4.6-mm × 25-cm; 10-μm packing L51

Column temperature: 30°

Injection size: 20 μL

System suitability

[Note—The relative retention times for trans-abacavir, abacavir enantiomer, and abacavir are 0.8, 0.9, and 1.0, respectively.]

Sample: System suitability solution

Suitability requirements

Resolution: NLT 1.0 between trans-abacavir and abacavir enantiomer; NLT 1.5 between abacavir enantiomer and abacavir

Analysis

Sample: Sample solution

Calculate the percentage of abacavir enantiomer in the portion of Abacavir Sulfate taken:

Result = (r_U/r_T) × 100

r_U = peak area of abacavir enantiomer from the Sample solution

r_T= total peak areas of abacavir and abacavir enantiomer from the Sample solution

Acceptance criteria

Individual impurities: NMT 0.3% of abacavir enantiomer

5 SPECIFIC TESTS

Water Determination, Method Ic〈921〉: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at room temperature.

USP Reference Standards 〈11〉

USP Abacavir Sulfate RS

USP Abacavir Stereoisomers Mixture RS

A mixture of abacavir sulfate, abacavir enantiomer, and trans-abacavir.

USP Abacavir Related Compounds Mixture RS

A mixture of abacavir glutarate, O-pyrimidine derivative abacavir, descyclopropyl abacavir, trans-abacavir, and t-butyl derivative abacavir.