Printed on: Tue Aug 03 2021, 07:38:43 AM Official Status: Currently Official on 03-Aug-2021 DocId: 1_GUID-FD764B8C-D819-4D50-B7C3-3C3BD478D310_1_en-US

(EST)
Printed by: Le Tran Official Date: Official Prior to 2013 Document Type: USP @2021 USPC
1

Mobile phase. [NOTE—Sonicate for 10 min before making final

Zidovudine Oral Solution
DEFINITION
Zidovudine Oral Solution contains NLT 90.0% and NMT
110.0% of the labeled amount of zidovudine (C10H13N5O4).
IDENTIFICATION
• The retention time of the zidovudine peak of the Sample
solution corresponds to that of the Standard solution, as
obtained in the Assay.
ASSAY
• PROCEDURE
Mobile phase: Methanol, acetonitrile, glacial acetic acid,
and 0.040 M sodium acetate (90:10:2:900)
Standard stock solution: 1 mg/mL of USP Zidovudine RS in
Mobile phase
Zidovudine related compound C stock solution:
0.1 mg/mL of USP Zidovudine Related Compound C RS in
Mobile phase. [NOTE—Sonicate for 10 min before making
final volume.]
Standard solution: Transfer 10.0 mL of the Standard stock
solution and 2.0 mL of the Zidovudine related compound C
volume.]
Standard solution: Transfer 10.0 mL of the Standard stock
solution and 2.0 mL of the Zidovudine related compound C
stock solution to a 100-mL volumetric flask. Dilute with
Mobile phase to volume, and mix.
Sample solution: Equivalent to 0.1 mg/mL of zidovudine in
Mobile phase
Chromatographic system and System suitability: Proceed
as directed in the Assay.
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of zidovudine related
compound C (thymine) in the portion of Oral Solution
taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak response from the Sample solution
rS = peak response from the Standard solution
CS = concentration of USP Zidovudine Related
Compound C RS in the Standard solution

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(mg/mL)
stock solution to a 100-mL volumetric flask. Dilute with CU = nominal concentration of zidovudine in the
Mobile phase to volume. Sample solution (mg/mL)
Sample solution: Equivalent to 0.1 mg/mL of zidovudine in
Mobile phase Acceptance criteria: NMT 3.0%
Chromatographic system • Procedure 2
(See Chromatography á621ñ, System Suitability.)
Mode: LC
Detector: UV 240 nm
ci Buffer: 5.44 mg/mL of sodium acetate trihydrate in water.
Pass the solution through a suitable filter of 0.45-µm
pore size.
Column: 4.0-mm × 12.5-cm; packing L1 Mobile phase: Methanol, acetonitrile, glacial acetic acid, and
Flow rate: 1 mL/min Buffer (50:10:2:940)
ffi
Injection size: 10 µL Standard stock solution: 0.25 mg/mL of USP Zidovudine RS
System suitability in Mobile phase. [NOTE—Sonicate to dissolve if necessary.]
Sample: Standard solution Standard solution: 0.002 mg/mL of USP Zidovudine RS in
[NOTE—The relative retention times for zidovudine Mobile phase from the Standard stock solution
related compound C and zidovudine are about Impurity stock solution: 0.625 mg/mL of USP Zidovudine
0.12 and 1.0, respectively.] Related Compound C RS, 0.375 mg/mL of thymidine,
O

Suitability requirements 0.375 mg/mL of USP Stavudine RS, and 0.25 mg/mL of USP
Resolution: NLT 4.0 between zidovudine and zidovudine Zidovudine Related Compound B RS dissolved initially at
related compound C 25% of final volume with methanol. Dilute with Mobile phase
Tailing factor: NMT 2.0 to final volume. [NOTE—Sonicate with intermittent shaking to
Relative standard deviation: NMT 2.0% dissolve, if necessary, and cool to room temperature before
Analysis diluting to final volume.]
Samples: Standard solution and Sample solution Impurity solution: 0.05 mg/mL of USP Zidovudine Related
Calculate the percentage of C10H13N5O4 in the portion of Compound C RS, 0.03 mg/mL of thymidine, 0.03 mg/mL of
Oral Solution taken: USP Stavudine RS, and 0.02 mg/mL of USP Zidovudine
Related Compound B RS in Mobile phase from the Impurity
Result = (rU/rS) × (CS/CU) × 100 stock solution
System suitability solution: 1 mg/mL of USP Zidovudine RS,
rU = peak response from the Sample solution 0.005 mg/mL of USP Zidovudine Related Compound C RS,
rS = peak response from the Standard solution 0.003 mg/mL of thymidine, 0.003 mg/mL of USP
CS = concentration of the Standard solution (mg/mL) Stavudine RS, 0.002 mg/mL of USP Zidovudine Related
CU = nominal concentration of zidovudine in the Compound B RS in Mobile phase from USP Zidovudine RS
Sample solution (mg/mL) and the Impurity solution
Sample solution: Equivalent to 1 mg/mL of zidovudine in
Acceptance criteria: 90.0%–110.0% Mobile phase
Chromatographic system
IMPURITIES
(See Chromatography á621ñ, System Suitability.)
ORGANIC IMPURITIES
Mode: LC
[NOTE—On the basis of the synthetic route, perform
Detector: UV 240 nm
either Procedure 1 or Procedure 2.]
Column: 4.6-mm × 10-cm; 3-µm packing L1
• Procedure 1
Column temperature: 25°
Mobile phase: Methanol, acetonitrile, glacial acetic acid, and
Flow rate: 1.5 mL/min
0.040 M sodium acetate (90:10:2:900)
Injection size: 20 µL
Standard stock solution: 1 mg/mL of USP Zidovudine RS in
System suitability
Mobile phase
Samples: Standard solution and System suitability solution
Zidovudine related compound C stock solution:
0.1 mg/mL of USP Zidovudine Related Compound C RS in

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Printed on: Tue Aug 03 2021, 07:38:43 AM Official Status: Currently Official on 03-Aug-2021 DocId: 1_GUID-FD764B8C-D819-4D50-B7C3-3C3BD478D310_1_en-US
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Printed by: Le Tran Official Date: Official Prior to 2013 Document Type: USP @2021 USPC
2

[NOTE—The relative retention times are listed in Impurity Impurity Table 1 (continued)
Table 1.] Relative Relative Acceptance
Suitability requirements Retention Response Criteria,
Resolution: NLT 1.4 between zidovudine and zidovudine Name Time Factor NMT (%)
related compound B, System suitability solution Individual unspecified impuri-
Tailing factor: NMT 2.0, Standard solution — 1.0 0.20
ty
Relative standard deviation: NMT 5.0%
a 5-Methylpyrimidine-2,4(1H,3H)-dione.
Analysis
b [1-(2-Deoxy-β-D-ribofuranosyl)]thymine.
Samples: Standard solution and Sample solution
c Thymidine, 2’,3’-didehydro-3’-deoxy-.
Calculate the percentage of each impurity in the portion of d 3’-Chloro-3’-deoxythymidine.
Oral Solution taken:

Result = (rU/rS) × (CS/CU) × 1/F × 100 SPECIFIC TESTS

• MICROBIAL ENUMERATION TESTS á61ñ and TESTS FOR
rU = peak response of each impurity in the Sample SPECIFIED MICROORGANISMS á62ñ: Meets the requirements
solution of the tests for absence of Salmonella species,
rS = peak response of zidovudine in the Standard Escherichia coli, Staphylococcus aureus, and Pseudomonas
solution aeruginosa
CS = concentration of USP Zidovudine RS in the • PH á791ñ: 3.0–4.0, in a mixture containing a volume of Oral
Standard solution (mg/mL) Solution equivalent to 150 mg of zidovudine and 5 mL of
CU = nominal concentration of zidovudine in the 0.12 M potassium chloride (3:1)
Sample solution (mg/mL) PERFORMANCE TESTS
F = relative response factor for each impurity (see

al
• DELIVERABLE VOLUME á698ñ: Meets the requirements for
Impurity Table 1) oral solution packaged in multiple-unit containers
• UNIFORMITY OF DOSAGE UNITS á905ñ: Meets the
Acceptance criteria
requirements for oral solution packaged in single-unit
Individual impurities: See Impurity Table 1.
containers
Total impurities: NMT 2.0%. [NOTE—All impurities listed in
Impurity Table 1 excluding zidovudine related
compound C]
ci ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight, light-resistant
containers.
Impurity Table 1 • LABELING: If a test for Organic Impurities other than
Relative Relative Acceptance Procedure 1 is used, then the labeling states with which
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Retention Response Criteria, Organic Impurities test the article complies.
Name Time Factor NMT (%) • USP REFERENCE STANDARDS á11ñ
Zidovudine related USP Stavudine RS
0.08 1.9 3.0
compound Ca USP Zidovudine RS
USP Zidovudine Related Compound B RS
Zidovudine (thymidine)b 0.14 1.0 0.30
3′-Chloro-3′-deoxythymidine.
O

Stavudinec 0.27 1.0 0.30 C10H13ClN2O4 260.68

Zidovudine 1.00 — —
USP Zidovudine Related Compound C RS
Thymine.
Zidovudine related
1.22 1.0 0.20 C5H6N2O2 126.12
compound Bd

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