Printed on: Wed Feb 08 2023, 11:20:30 PM(EST) Status: Currently Official on 09-Feb-2023 DocId: GUID-31F184CC-1F1E-4C7F-A971-EF2B81BAF247_1_en-US

Printed by: Dang Van Vu Official Date: Official as of 01-Aug-2016 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: 91mgt DOI: https://doi.org/10.31003/USPNF_M3876_01_01
1

Abacavir and Lamivudine Tablets
DEFINITION
Abacavir and Lamivudine Tablets contain an amount of
abacavir sulfate and lamivudine equivalent to NLT 90.0%
and NMT 110.0% of the labeled amount of abacavir
(C14H18N6O) and NLT 90.0% and NMT 110.0% of the
labeled amount of lamivudine (C8H11N3O3S), respectively.
IDENTIFICATION
• A. The retention times of the major peaks of the Sample
solution correspond to those of the Standard solution, as
obtained in the Assay.
ASSAY
• PROCEDURE
Diluent: 0.1 N hydrochloric acid
Solution A: Water and trifluoroacetic acid (2000:1)
Solution B: Acetonitrile, methanol, and trifluoroacetic acid
(1000:1000:1)
Mobile phase: See Table 1. [NOTE—Return to original
conditions and re-equilibrate the system for about 7 min.]
Suitability requirements
Resolution: NLT 1.0 between lamivudine-S-oxide and
lamivudine-R-oxide; NLT 1.0 between lamivudine
diastereomer and lamivudine, System suitability solution
Relative standard deviation: NMT 1.5% each for
abacavir and lamivudine, Standard solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of abacavir
(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 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 multiplied by 2,
572.66

al
Table 1 Mr2 = molecular weight of abacavir sulfate, 670.74
Time Solution A Solution B
(min) (%) (%) Acceptance criteria: 90.0%–110.0% of the labeled amount
0 100 0 of abacavir
Calculate the percentage of the labeled amount of
4

12
100

70
0

30
ci lamivudine (C8H11N3O3S) in the portion of Tablets taken:

Result = (rU/rS) × (CS/CU) × 100

12.1 40 60

13.1 40 60 rU = peak response of lamivudine from the Sample

ffi
solution
13.2 100 0 rS = peak response of lamivudine from the Standard
solution
System suitability solution: Dissolve the contents of one CS = concentration of USP Lamivudine RS in the
vial of USP Lamivudine Resolution Mixture C RS in 2.5 mL Standard solution (mg/mL)
of Diluent. [NOTE—One vial of USP Lamivudine Resolution CU = nominal concentration of lamivudine in the
O

Mixture C RS contains 0.8 mg of USP Lamivudine Sample solution (mg/mL)

Resolution Mixture C RS.]
Standard solution: 0.35 mg/mL of USP Abacavir Sulfate RS Acceptance criteria: 90.0%–110.0% of the labeled amount
and 0.15 mg/mL of USP Lamivudine RS in Diluent. Sonicate of lamivudine
to dissolve prior to final dilution. PERFORMANCE TESTS
Sample stock solution: Nominally 3 mg/mL of abacavir and • DISSOLUTION á711ñ
1.5 mg/mL of lamivudine in Diluent prepared as follows. Medium: 0.1 N hydrochloric acid; 900 mL
Transfer NLT 5 Tablets to a suitable volumetric flask. Add Apparatus 2: 75 rpm
Diluent to about 50% of the final volume and shake for NMT Time: 30 min
30 min to disperse the Tablets. Dilute with Diluent to Standard solution 1: 0.79 mg/mL of USP Abacavir
volume. Pass through a suitable filter. Sulfate RS in Medium. Sonicate to dissolve prior to final
Sample solution: Nominally 0.3 mg/mL of abacavir and dilution.
0.15 mg/mL of lamivudine in Diluent from Sample stock Standard solution 2: 0.33 mg/mL of USP Lamivudine RS in
solution Medium. Sonicate to dissolve prior to final dilution.
Chromatographic system Sample solution: Pass a portion of the solution under test
(See Chromatography á621ñ, System Suitability.) through a suitable filter.
Mode: LC Instrumental conditions
Detector: UV 270 nm Mode: UV
Column: 4.6-mm × 15-cm; 3.5-µm packing L1 Wavelength: 240–320 nm
Column temperature: 40° Cell length: 0.2 mm
Flow rate: 1.5 mL/min Blank: Medium
Injection volume: 10 µL Analysis: The calculations of the percentages dissolved are
System suitability performed using multi-component analysis software.
Samples: System suitability solution and Standard solution Tolerances: NLT 80% (Q) of the labeled amount of abacavir
[NOTE—The relative retention times for and lamivudine is dissolved.
lamivudine-S-oxide and lamivudine-R-oxide, in • UNIFORMITY OF DOSAGE UNITS á905ñ: Meet the
relation to the lamivudine peak, are 0.31 and 0.36, requirements
respectively; the relative retention times for
lamivudine diastereomer and lamivudine are
0.88 and 1.0, respectively; System suitability solution.]

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Printed on: Wed Feb 08 2023, 11:20:30 PM(EST) Status: Currently Official on 09-Feb-2023 DocId: GUID-31F184CC-1F1E-4C7F-A971-EF2B81BAF247_1_en-US
Printed by: Dang Van Vu Official Date: Official as of 01-Aug-2016 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: 91mgt DOI: https://doi.org/10.31003/USPNF_M3876_01_01
2

IMPURITIES Table 2 (continued)

• ORGANIC IMPURITIES Relative Acceptance
Diluent, Solution A, Solution B, Mobile phase, System Retention Criteria,
suitability solution, Standard solution, Sample stock Name Time NMT (%)
solution, Sample solution, Chromatographic system, Total lamivudine related
and System suitability: Proceed as directed in the Assay. —
impuritiesk 0.6
Analysis
Total abacavir related
Sample: Sample solution impuritiesl
—
1.0
Calculate the percentage of each individual abacavir related
impurity and each unspecified impurity in the portion of a 4-Aminopyrimidin-2(1H)-one (lamivudine related impurity).
Tablets taken: b 1-[(2R,3S,5S)-2-(Hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine S-oxide.
c 1-[(2R,3R,5S)-2-(Hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine S-oxide.
Result = (rU/rT) × 100 d (2RS,5SR)-5-(Cytosine-1-yl)-1,3-oxathiolane-2-carboxylic acid.
e Process impurity monitored in the drug substance.
rU = peak response of each abacavir related impurity f 1-[(2S,5S)-2-(Hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine.
or unspecified impurity g 1-[(2RS,5SR)-2-(Hydroxymethyl)-1,3-oxathiolan-5-yl]uracil.
rT = sum of the peak responses of abacavir, all abacavir h N6-Cyclopropyl-9H-purine-2,6-diamine.
i [(1S,4R)-4-(2,6-Diamino-9H-purin-9-yl)cyclopent-2-enyl]methanol.
related impurities, and all unspecified impurities
j (1R,2R,4S)-2-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]-4-

Calculate the percentage of each lamivudine related (hydroxymethyl)cyclopentan-1-ol.

k Includes all lamivudine related impurities.
impurity in the portion of Tablets taken: l Includes all abacavir related and all individual unspecified impurities.

Result = (rU/rT) × 100

al
ADDITIONAL REQUIREMENTS
rU = peak response of each lamivudine related • PACKAGING AND STORAGE: Preserve in tight, light-resistant
impurity containers. Store at controlled room temperature.
rT = sum of the peak responses of lamivudine and all • USP REFERENCE STANDARDS á11ñ
lamivudine related impurities ci USP Abacavir Sulfate RS
USP Lamivudine RS
Acceptance criteria: See Table 2. Disregard any peak less USP Lamivudine Resolution Mixture C RS
than 0.05%. This is a mixture of lamivudine and the following
impurities (other impurities may also be present).
Table 2 Uracil: Pyrimidine-2,4(1H,3H)-dione.
C4H4N2O2 112.09
ffi
Relative Acceptance
Retention Criteria, Lamivudine-uracil derivative: 1-[(2RS,5SR)-2-
Name Time NMT (%) (Hydroxymethyl)-1,3-oxathiolan-5-yl]uracil.
Cytosine a
0.12 0.2
C8H10N2O4S 230.24
Cytosine: 4-Aminopyrimidin-2(1H)-one.
Lamivudine-S-sulfoxideb 0.19 0.2 C4H5N3O 111.10
O

Lamivudine-R-sulfoxidec 0.21 0.2 Lamivudine-S-sulfoxide: 1-[(2R,3S,5S)-2-

(Hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine S-oxide.
Lamivudine-carboxylic acidd 0.49 —e C8H11N3O4S 245.26
Lamivudine diastereomer (Lamivu- Lamivudine-R-sulfoxide: 1-[(2R,3R,5S)-2-
—e
dine-trans)f 0.52 (Hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine S-oxide.
Lamivudine 0.60 —
C8H11N3O4S 245.26
Lamivudine carboxylic acid: (2RS,5SR)-5-(Cytosine-1-yl)-
Lamivudine-uracil derivative g
0.78 0.2 1,3-oxathiolane-2-carboxylic acid.
Cyclopropyldiaminopurine C8H9N3O4S 243.24
abacavirh 0.80 0.2 Lamivudine diastereomer: 1-[(2S,5S)-2-(Hydroxymethyl)-
i
1,3-oxathiolan-5-yl]cytosine.
Descyclopropyl abacavir 0.85 0.2
C8H11N3O3S 229.26
3-Hydroxyabacavirj 0.89 —e Salicylic acid: 2-Hydroxybenzoic acid.
Abacavir 1.0 —e
C7H6O3 138.12

Any individual unspecified

—
impurity 0.2

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