11/27/2020 USP-NF Abacavir Sulfate

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O cial Date: O cial as of 1-May-2020
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© 2020 USPC

Abacavir Sulfate

(C14H18N6O)2 · 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) [188062-50-2]; UNII: 
J220T4J9Q2.

DEFINITION
Abacavir Sulfate contains NLT 97.0% and NMT 102.0% of (C14H18N6O)2 · H2SO4, calculated on the anhydrous and solvent-free basis.

IDENTIFICATION
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〉
Sample solution: 5 mg/mL
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ASSAY
• PROCEDURE
Mobile phase: Acetonitrile, phosphoric acid, and water (20:1:180)
Standard solution: 0.04 mg/mL of USP Abacavir Sulfate RS in water
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Sample solution: 0.04 mg/mL of Abacavir Sulfate in water

Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 254 nm
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Column: 4.6-mm × 5-cm; 5-µm packing L1

Column temperature: 30°
Flow rate: 1 mL/min
Injection size: 20 µL
System suitability
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Sample: Standard solution

Suitability requirements
Relative standard deviation: NMT 1.5%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of (C14H18N6O)2 · H2SO4 in the portion of Abacavir Sulfate taken:

Result = (rU/rS) × (CS/CU) × 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 = concentration of Abacavir Sulfate in the Sample solution (mg/mL)

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

IMPURITIES
INORGANIC IMPURITIES
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11/27/2020 USP-NF Abacavir Sulfate

• RESIDUE ON IGNITION 〈281〉: NMT 0.2%

ORGANIC IMPURITIES
• PROCEDURE 1: RELATED COMPOUNDS
Solution A: Tri uoroacetic acid and water (0.05:99.95)
Solution B: Methanol and water (17:3)
Mobile phase: See the gradient table below.

Time (min) Solution A (%) Solution B (%)

0 95 5

20 70 30

35 10 90

35.1 95 5

50 95 5

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
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Sample: System suitability solution
Suitability requirements
Resolution: NLT 1.5 between abacavir and trans-abacavir
Analysis
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Sample: Sample solution

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

Result = (rU/rT) × 100

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rU = peak area of each impurity from the Sample solution

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

Acceptance criteria
Individual impurities: See Impurity Table 1.
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Total impurities: NMT 0.8%

Impurity Table 1

Name Relative Retention Time Acceptance Criteria, NMT (%)

Descyclopropyl abacavira 0.65 0.2

Abacavir 1.00 —

trans-Abacavirb 1.04 0.2

O-Pyrimidine derivative abacavirc 1.33 0.2

t-Butyl derivative abacavird 1.67 0.2

Any unspeci ed impurity — 0.1

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.

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11/27/2020 USP-NF Abacavir Sulfate
c  N6-Cyclopropyl-9-{(1R,4S)-4-[(2,5-diamino-6-chloropyrimidin-4-yl oxy)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.

• 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.

Time (min) Solution A (%) Solution B (%) Flow Rate (mL/min)

0 100 0 1.0

25 100 0 1.0

27 0 100 0.8

37 0 100 0.8

39 100 0 1.0

55 100 0 1.0

Diluent: Methanol and tri uoroacetic 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

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fully dissolved. Add 3 mL of 2-propanol, mix, and dilute with heptane to volume.
Chromatographic system
IA
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 286 nm
Column: 4.6-mm × 25-cm; 10-µm packing L51
Column temperature: 30°
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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
FF

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:
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Result = (rU/rT) × 100

rU = peak area of abacavir enantiomer from the Sample solution

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

Acceptance criteria
Individual impurities: NMT 0.3% of abacavir enantiomer

SPECIFIC TESTS
• WATER DETERMINATION, Method Ic〈921〉: NMT 0.5%

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.

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11/27/2020 USP-NF Abacavir Sulfate

Auxiliary Information- Please check for your question in the FAQs before contacting USP.

Topic/Question Contact Expert Committee

ABACAVIR SULFATE Shankari Shivaprasad SM12020 Small Molecules 1

Senior Scienti c Liaison

Chromatographic Database Information: Chromatographic Database

Most Recently Appeared In:

Pharmacopeial Forum: Volume No. 36(3)

Page Information:

USP43-NF38 - 23
USP42-NF37 - 25
USP41-NF36 - 23

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