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6414 Zidovudine / Official Monographs
IDENTIFICATION
• A. ULTRAVIOLET ABSORPTION 〈197U〉
Solution A: Methanol and water (75:25)
Sample solution: Nominally 15 µg/mL of zidovudine
from Injection in Solution A
Acceptance criteria: Meets the requirements
• B. 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
Mobile phase: Methanol and water (20:80)
Standard stock solution: 1.0 mg/mL of USP
Zidovudine RS in methanol
Zidovudine related compound C standard stock solu-
tion: 0.2 mg/mL of USP Zidovudine Related Com-
pound C RS in methanol prepared as follows. Transfer
20 mg of USP Zidovudine Related Compound C RS to a
100-mL volumetric flask, add 75 mL of methanol, soni-
cate for 15 min, and dilute with methanol to volume.
Standard solution: 0.1 mg/mL of USP Zidovudine RS
and 4 µg/mL of USP Zidovudine Related Compound C
RS prepared as follows. Transfer a suitable volume of
Standard stock solution and Zidovudine related compound
C standard stock solution to a suitable volumetric flask.
Add 25% of the flask volume of water, and dilute with
methanol to volume.
Sample solution: Nominally 0.1 mg/mL of zidovudine
from Injection in Mobile phase
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 265 nm
Columns
Guard: Recommended dimensions are 3.2-mm × 1.5-
cm; packing L1.
Analytical: 4.0-mm × 25-cm; packing L1
USP Monographs
Flow rate: 1 mL/min
Injection volume: 10 µL
System suitability
Sample: Standard solution
[NOTE—The relative retention times for zidovudine re-
lated compound C and zidovudine are about 0.2 and
1.0, respectively.]
Suitability requirements
Resolution: NLT 5.0 between zidovudine and
zidovudine related compound C
Tailing factor: NMT 1.5 for the zidovudine peak
Relative standard deviation: NMT 2.0% for the
zidovudine peak
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of
zidovudine (C10H13N5O4) in the portion of Injection
taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak response of zidovudine from the Sample
solution
rS = peak response of zidovudine from the
Standard solution
CS = concentration of the Standard solution
(mg/mL)
CU = nominal concentration of zidovudine in the
Sample solution (mg/mL)
Acceptance criteria: 90.0%–110.0%
IMPURITIES
• ORGANIC IMPURITIES
Mobile phase, Standard stock solution, Zidovudine re-
lated compound C standard stock solution, Sample
solution, Chromatographic system, and System suita-
bility: Proceed as directed in the Assay.
Official from May 1, 2016
Copyright (c) 2016 The United States Pharmacopeial Convention. All rights reserved.
USP 39
Standard solution: 0.1 mg/mL of USP Zidovudine RS
and 2 µg/mL of USP Zidovudine Related Compound C
RS prepared as follows. Transfer a suitable volume of
Standard stock solution and Zidovudine related compound
C standard stock solution to a suitable volumetric flask.
Add 25% of the flask volume of water, and dilute with
methanol to volume.
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of zidovudine related com-
pound C in the portion of Injection taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak response of zidovudine related
compound C from the Sample solution
rS = peak response of zidovudine related
compound C from the Standard solution
CS = concentration of USP Zidovudine Related
Compound C RS in the Standard solution
(mg/mL)
CU = nominal concentration of zidovudine in the
Sample solution (mg/mL)
Acceptance criteria: NMT 1.0%
SPECIFIC TESTS
• STERILITY TESTS 〈71〉: Meets the requirement when tested
as directed in Test for Sterility of the Product to Be Ex-
amined, Membrane Filtration
• PH 〈791〉
Sample solution: A mixture containing a volume of In-
jection equivalent to 150 mg of zidovudine and 5 mL of
0.12 M potassium chloride
Acceptance criteria: 3.5–7.0
• BACTERIAL ENDOTOXINS TEST 〈85〉: NMT 1.0 USP Endo-
toxin Unit/mg of zidovudine
Change to read:
• OTHER REQUIREMENTS: Meets the requirements in •Injec-
.
tions and Implanted Drug Products 〈1〉• (CN 1-May-2016)
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight, light-resistant
containers.
• USP REFERENCE STANDARDS 〈11〉
USP Endotoxin RS
USP Zidovudine RS
USP Zidovudine Related Compound C RS
Thymine.
C5H6N2O2 126.12
.
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
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USP 39 Official Monographs / Zidovudine 6415

in Mobile phase. [NOTE—Sonicate for 10 min before CU = nominal concentration of zidovudine in the
making final volume.] Sample solution (mg/mL)
Standard solution: Transfer 10.0 mL of the Standard Acceptance criteria: NMT 3.0%
stock solution and 2.0 mL of the Zidovudine related com- • PROCEDURE 2
pound C stock solution to a 100-mL volumetric flask. Di- Buffer: 5.44 mg/mL of sodium acetate trihydrate in
lute with Mobile phase to volume. water. Pass the solution through a suitable filter of
Sample solution: Equivalent to 0.1 mg/mL of 0.45-µm pore size.
zidovudine in Mobile phase Mobile phase: Methanol, acetonitrile, glacial acetic
Chromatographic system acid, and Buffer (50:10:2:940)
(See Chromatography 〈621〉, System Suitability.) Standard stock solution: 0.25 mg/mL of USP
Mode: LC Zidovudine RS in Mobile phase. [NOTE—Sonicate to dis-
Detector: UV 240 nm solve if necessary.]
Column: 4.0-mm × 12.5-cm; packing L1 Standard solution: 0.002 mg/mL of USP Zidovudine
Flow rate: 1 mL/min RS in Mobile phase from the Standard stock solution
Injection size: 10 µL Impurity stock solution: 0.625 mg/mL of USP
System suitability Zidovudine Related Compound C RS, 0.375 mg/mL of
Sample: Standard solution thymidine, 0.375 mg/mL of USP Stavudine RS, and
[NOTE—The relative retention times for zidovudine re- 0.25 mg/mL of USP Zidovudine Related Compound B
lated compound C and zidovudine are about 0.12 and RS dissolved initially at 25% of final volume with meth-
1.0, respectively.] anol. Dilute with Mobile phase to final volume. [NOTE—
Suitability requirements Sonicate with intermittent shaking to dissolve, if neces-
Resolution: NLT 4.0 between zidovudine and sary, and cool to room temperature before diluting to
zidovudine related compound C final volume.]
Tailing factor: NMT 2.0 Impurity solution: 0.05 mg/mL of USP Zidovudine Re-
Relative standard deviation: NMT 2.0% lated Compound C RS, 0.03 mg/mL of thymidine,
Analysis 0.03 mg/mL of USP Stavudine RS, and 0.02 mg/mL of
Samples: Standard solution and Sample solution USP Zidovudine Related Compound B RS in Mobile
Calculate the percentage of C10H13N5O4 in the portion phase from the Impurity stock solution
of Oral Solution taken: System suitability solution: 1 mg/mL of USP
Zidovudine RS, 0.005 mg/mL of USP Zidovudine Re-
Result = (rU/rS) × (CS/CU) × 100 lated Compound C RS, 0.003 mg/mL of thymidine,
0.003 mg/mL of USP Stavudine RS, 0.002 mg/mL of
rU = peak response from the Sample solution USP Zidovudine Related Compound B RS in Mobile
rS = peak response from the Standard solution phase from USP Zidovudine RS and the Impurity
CS = concentration of the Standard solution solution
(mg/mL) Sample solution: Equivalent to 1 mg/mL of zidovudine
CU = nominal concentration of zidovudine in the in Mobile phase
Sample solution (mg/mL) Chromatographic system

USP Monographs
Acceptance criteria: 90.0%–110.0% (See Chromatography 〈621〉, System Suitability.)
Mode: LC
IMPURITIES Detector: UV 240 nm
Organic Impurities Column: 4.6-mm × 10-cm; 3-µm packing L1
[NOTE—On the basis of the synthetic route, perform either Column temperature: 25°
Procedure 1 or Procedure 2.] Flow rate: 1.5 mL/min
• PROCEDURE 1 Injection size: 20 µL
Mobile phase: Methanol, acetonitrile, glacial acetic System suitability
acid, and 0.040 M sodium acetate (90:10:2:900) Samples: Standard solution and System suitability
Standard stock solution: 1 mg/mL of USP Zidovudine solution
RS in Mobile phase [NOTE—The relative retention times are listed in Impu-
Zidovudine related compound C stock solution: rity Table 1.]
0.1 mg/mL of USP Zidovudine Related Compound C RS Suitability requirements
in Mobile phase. [NOTE—Sonicate for 10 min before Resolution: NLT 1.4 between zidovudine and
making final volume.] zidovudine related compound B, System suitability
Standard solution: Transfer 10.0 mL of the Standard solution
stock solution and 2.0 mL of the Zidovudine related com- Tailing factor: NMT 2.0, Standard solution
pound C stock solution to a 100-mL volumetric flask. Relative standard deviation: NMT 5.0%
Dilute with Mobile phase to volume, and mix. Analysis
Sample solution: Equivalent to 0.1 mg/mL of Samples: Standard solution and Sample solution
zidovudine in Mobile phase Calculate the percentage of each impurity in the por-
Chromatographic system and System suitability: Pro- tion of Oral Solution taken:
ceed as directed in the Assay.
Analysis Result = (rU/rS) × (CS/CU) × 1/F × 100
Samples: Standard solution and Sample solution
Calculate the percentage of zidovudine related com- rU = peak response of each impurity in the Sample
pound C (thymine) in the portion of Oral Solution solution
taken: rS = peak response of zidovudine in the Standard
solution
Result = (rU/rS) × (CS/CU) × 100 CS = concentration of USP Zidovudine RS in the
Standard solution (mg/mL)
rU = peak response from the Sample solution CU = nominal concentration of zidovudine in the
rS = peak response from the Standard solution Sample solution (mg/mL)
CS = concentration of USP Zidovudine Related F = relative response factor for each impurity (see
Compound C RS in the Standard solution Impurity Table 1)
(mg/mL)

Official from May 1, 2016

Copyright (c) 2016 The United States Pharmacopeial Convention. All rights reserved.
 Accessed from 10.6.1.1 by merck1 on Fri Jun 03 04:46:16 EDT 2016

6416 Zidovudine / Official Monographs USP 39

Acceptance criteria Acceptance criteria: Meet the requirements

Individual impurities: See Impurity Table 1. • B. The retention time of the major peak of the Sample
Total impurities: NMT 2.0%. [NOTE—All impurities solution corresponds to that of the Standard solution, as
listed in Impurity Table 1 excluding zidovudine related obtained in the Assay.
compound C]
ASSAY
• PROCEDURE
Impurity Table 1
Mobile phase: Dissolve 3.0 g of sodium acetate and
Relative Accep- 1.3 g of sodium 1-octane sulfonate in 900 mL of water.
Reten- Relative tance Add 90 mL of methanol and 40 mL of acetonitrile. Ad-
tion Response Criteria, just with glacial acetic acid to a pH of 5.3.
Name Time Factor NMT (%) Zidovudine related compound B standard stock solu-
Zidovudine related tion: 0.1 mg/mL of USP Zidovudine Related Com-
0.08 1.9 3.0 pound B RS in methanol
compound Ca
Zidovudine related compound C standard stock solu-
.

Zidovudine
(thymidine)b
0.14 1.0 0.30 tion: 0.2 mg/mL of USP Zidovudine Related Com-
pound C RS in methanol prepared as follows. Dissolve
.

Stavudinec 0.27 1.0 0.30

.

by sonicating for 15 min before bringing the solution to

Zidovudine 1.00 — — volume.
Zidovudine related
1.22 1.0 0.20 Standard solution: 0.12 mg/mL of USP Zidovudine RS,
compound Bd .

1 µg/mL of USP Zidovudine Related Compound B RS,

Individual unspecified and 4 µg/mL of USP Zidovudine Related Compound C
— 1.0 0.20
impurity RS prepared as follows. Transfer 30 mg of USP
a 5-Methylpyrimidine-2,4(1H,3H)-dione. Zidovudine RS to a 250-mL volumetric flask, and dis-
solve in 3.0 mL of methanol. Add 2.5 mL of Zidovudine
.

b [1-(2-Deoxy-β-D-ribofuranosyl)]thymine.
related compound B standard stock solution and 5.0 mL
.

c Thymidine, 2’,3’-didehydro-3’-deoxy-.

of Zidovudine related compound C standard stock solu-

.

d 3’-Chloro-3’-deoxythymidine.

tion, and dilute with water to volume.

.

SPECIFIC TESTS Sample stock solution: Nominally 3 mg/mL of

• MICROBIAL ENUMERATION TESTS 〈61〉 and TESTS FOR SPECI-
FIED MICROORGANISMS 〈62〉: Meets the requirements of
the tests for absence of Salmonella species, Escherichia
coli, Staphylococcus aureus, and Pseudomonas aeruginosa
• PH 〈791〉: 3.0–4.0, in a mixture containing a volume of
Oral Solution equivalent to 150 mg of zidovudine and
5 mL of 0.12 M potassium chloride (3:1)
PERFORMANCE TESTS
USP Monographs
zidovudine prepared as follows. Transfer a number of
Tablets, equivalent to 1500 mg of zidovudine, to a
500-mL volumetric flask. Add 50 mL of water, and
shake by mechanical means for 30 min to disperse the
Tablets. Add 150 mL of methanol, and sonicate for 10
min. Dilute with water to volume.
Sample solution: Nominally 0.12 mg/mL of zidovudine
in water from Sample stock solution. Pass the solution
through a nylon filter, discarding the first 2 mL of the

• DELIVERABLE VOLUME 〈698〉: Meets the requirements for filtrate.

oral solution packaged in multiple-unit containers Chromatographic system
• UNIFORMITY OF DOSAGE UNITS 〈905〉: Meets the require- (See Chromatography 〈621〉, System Suitability.)
ments for oral solution packaged in single-unit containers Mode: LC
ADDITIONAL REQUIREMENTS Detector: UV 265 nm
• PACKAGING AND STORAGE: Preserve in tight, light-resistant Column: 4.6-mm × 15-cm; packing L1
containers. Flow rate: 1.3 mL/min
• LABELING: If a test for Organic Impurities other than Proce- Injection volume: 20 µL
dure 1 is used, then the labeling states with which Or- System suitability
ganic Impurities test the article complies. Sample: Standard solution
• USP REFERENCE STANDARDS 〈11〉 [NOTE—The relative retention times for zidovudine re-
USP Stavudine RS lated compound C, zidovudine, and zidovudine related
USP Zidovudine RS compound B are about 0.17, 1.0, and 1.2,
USP Zidovudine Related Compound B RS respectively.]
3′-Chloro-3′-deoxythymidine. Suitability requirements
C10H13ClN2O4 260.68 Resolution: NLT 2.5 between the zidovudine and
USP Zidovudine Related Compound C RS zidovudine related compound B peaks
Thymine. Tailing factor: NMT 2.0 for the zidovudine peak
C5H6N2O2 126.12 Relative standard deviation: NMT 2.0% for the
zidovudine peak
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of
zidovudine (C10H13N5O4) in the portion of Tablets
.

Zidovudine Tablets taken:

DEFINITION Result = (rU/rS) × (CS/CU) × 100
Zidovudine Tablets contain NLT 90.0% and NMT 110.0% of
the labeled amount of zidovudine (C10H13N5O4). rU = peak response from the Sample solution
rS = peak response from the Standard solution
IDENTIFICATION CS = concentration of USP Zidovudine RS in the
• A. INFRARED ABSORPTION 〈197K〉 Standard solution (mg/mL)
Sample: Grind 1 Tablet in a mortar so that no large CU = nominal concentration of zidovudine in the
pieces remain, and remove the coating film so that Sample solution (mg/mL)
about 5 mg of ground Tablet remain.

Official from May 1, 2016

Copyright (c) 2016 The United States Pharmacopeial Convention. All rights reserved.