Accessed from 10.6.1.
1 by merck1 on Fri Jun 03 04:45:49 EDT 2016
6412 Zidovudine / Official Monographs
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 USP Zidovudine RS,
1 µg/mL of USP Zidovudine Related Compound B RS,
and 2 µg/mL of USP Zidovudine Related Compound C
RS in methanol from an appropriate volume of Standard
stock solution, Zidovudine related compound B standard
stock solution, and Zidovudine related compound C stan-
dard stock solution, respectively.
Sample solution: 0.1 mg/mL of Zidovudine in
methanol
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 265 nm
Columns
Guard: With recommended dimensions of 3.2-mm ×
1.5-cm; packing L1
Analytical: 4.0-mm × 25-cm; packing L1
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, zidovudine, and zidovudine related
compound B are 0.25, 1.0, and 1.17, respectively.]
Suitability requirements
Resolution: NLT 1.4 between the zidovudine and
zidovudine related compound B peaks
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 zidovudine (C10H13N5O4) in
the portion of Zidovudine taken:
Result = (rU/rS) × (CS/CU) × 100
USP Monographs
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 = concentration of the Sample solution (mg/mL)
Acceptance criteria: 97.0%–102.0% on the anhydrous
basis
IMPURITIES
• RESIDUE ON IGNITION 〈281〉: NMT 0.25%
• LIMIT OF TRIPHENYLMETHANOL AND OTHER IMPURITIES
Standard solution: 0.1 mg/mL each of USP Zidovudine
RS and triphenylmethanol in methanol
Sample solution: 20 mg/mL of Zidovudine in methanol
Chromatographic system
(See Chromatography 〈621〉, Thin-Layer Chromato-
graphy.)
Mode: TLC
Adsorbent: 0.25-mm layer of chromatographic silica
gel mixture containing a fluorescent indicator having
an optimal intensity at 254 nm
Application volume: 10 µL
Developing solvent system: Chloroform and metha-
nol (9:1)
Spray reagent: 5 mg/mL of carbazole in alcohol and
sulfuric acid (95:5)
Analysis: Develop the chromatogram until the solvent
front has moved three-fourths of the length of the
plate. Remove the plate from the chamber, mark the
solvent front, and allow the solvent to evaporate. Ex-
amine the plate under short-wavelength UV light, and
compare the intensities of any secondary spots ob-
served in the chromatogram of the Sample solution with
Official from May 1, 2016
Copyright (c) 2016 The United States Pharmacopeial Convention. All rights reserved.
USP 39
those of the principal spot in the chromatogram of the
Standard solution.
Acceptance criteria 1: No secondary spot from the
chromatogram of the Sample solution is larger or more
intense than the principal spot from the Standard solu-
tion, and the sum of the intensities of the secondary
spots obtained from the Sample solution corresponds
to NMT 3.0%.
Spray the plate with Spray reagent, heat for 10 min at
120°, and compare the intensities of any secondary
spots observed in the chromatogram of the Sample so-
lution with those of the principal spots in the chromat-
ogram of the Standard solution.
Acceptance criteria 2: No spot corresponding to
triphenylmethanol (RF about 2.3 relative to the RF of
zidovudine) is more intense than the corresponding
spot from the Standard solution. No secondary spot
from the chromatogram of the Sample solution is
larger or more intense than the principal spot ob-
tained from the Standard solution. The sum of the in-
tensities of the secondary spots from the Sample solu-
tion corresponds to NMT 3.0%.
• LIMIT OF ZIDOVUDINE RELATED COMPOUNDS B AND C
Mobile phase, Standard solution, Sample solution,
Chromatographic system, and System suitability:
Proceed as directed in the Assay.
Analysis
Sample: Sample solution
Calculate the percentage of zidovudine related com-
pound B and zidovudine related compound C in the
portion of Zidovudine taken:
Result = (rU/rT) × 100
rU = peak response for zidovudine related
compound B or zidovudine related
compound C
rT = sum of the responses of all of the peaks
Acceptance criteria
Individual impurities: NMT 1.0% for zidovudine re-
lated compound B and NMT 2.0% for zidovudine re-
lated compound C
Total impurities: NMT 3.0% for all impurities from
the tests for Limit of Triphenylmethanol and Other Impu-
rities and Limit of Zidovudine Related Compounds B and
C.
SPECIFIC TESTS
• WATER DETERMINATION, Method I 〈921〉: NMT 1.0%
• OPTICAL ROTATION, Specific Rotation 〈781S〉
Sample solution: 10 mg/mL, in alcohol
Acceptance criteria: +60.5° to +63°
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight, light-resistant
containers. Store at 25°, excursions permitted between
15° and 30°.
• USP REFERENCE STANDARDS 〈11〉
USP Zidovudine RS
USP Zidovudine Related Compound B RS
3′-Chloro-3′-deoxythymidine.
C10H13ClN2O4 260.68
USP Zidovudine Related Compound C RS
Thymine.
C5H6N2O2 126.12
.
Zidovudine Capsules
DEFINITION
Zidovudine Capsules contain NLT 90.0% and NMT 110.0%
of the labeled amount of zidovudine (C10H13N5O4).
Accessed from 10.6.1.1 by merck1 on Fri Jun 03 04:45:49 EDT 2016
USP 39
IDENTIFICATION
• A. ULTRAVIOLET ABSORPTION 〈197U〉
Solution A: Methanol and water (75:25)
Sample solution: 15 µg/mL prepared as follows. Mix
Capsule contents, equivalent to 300 mg of zidovudine,
with 50 mL of Solution A in a 200-mL volumetric flask.
Sonicate for 5 min, and dilute with methanol to vol-
ume. Allow insoluble solids to settle, and dilute the su-
pernatant 100-fold with Solution A.
Acceptance criteria: Meet 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)
Diluent: Methanol and water (75:25)
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, dilute with methanol to volume.
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 10 mL of Standard stock
solution and 1.0 mL of Zidovudine related compound C
standard stock solution to a 100-mL volumetric flask,
add 25 mL of water, and dilute with methanol to
volume.
Sample stock solution: Nominally 1 mg/mL of
zidovudine in Diluent prepared as follows. Weigh the
contents of Capsules (NLT 20), mix, and transfer a por-
tion of the powder, equivalent to 100 mg of
zidovudine, to a 100-mL volumetric flask. Dissolve in
Diluent, sonicate for 20 min, and dilute with Diluent to
volume. Allow the solids to settle, and use the superna-
tant layer to prepare the Sample solution.
Sample solution: Nominally 0.1 mg/mL of zidovudine
from a suitable volume of supernatant of Sample stock
solution in Diluent. Filter, discarding the first 4 mL of the
filtrate.
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
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 the zidovudine and
zidovudine related compound C peaks
Tailing factor: NMT 2.0 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 Capsules
taken:
Result = (rU/rS) × (CS/CU) × 100
Official from May 1, 2016
Copyright (c) 2016 The United States Pharmacopeial Convention. All rights reserved.
Official Monographs / Zidovudine 6413
rU = peak response of zidovudine from the Sample
solution
rS = peak response of zidovudine from the
Standard solution
CS = concentration of USP Zidovudine RS in the
Standard solution (mg/mL)
CU = nominal concentration of the Sample solution
(mg/mL)
Acceptance criteria: 90.0%–110.0%
PERFORMANCE TESTS
• DISSOLUTION 〈711〉
Medium: Water; 900 mL
Apparatus 2: 50 rpm
Time: 45 min
Mobile phase, Chromatographic system, and System
suitability: Proceed as directed in the Assay.
Standard solution: Prepare a solution having a known
concentration of USP Zidovudine RS in Medium.
Sample solution: A filtered portion of the solution
under test, suitably diluted with Medium
Analysis
Samples: Standard solution and Sample solution
Determine the percentage of zidovudine (C10H13N5O4)
dissolved by using the procedure set forth in the As-
say, making any necessary modifications.
Tolerances: NLT 75% (Q) of the labeled amount of
zidovudine (C10H13N5O4) is dissolved.
• UNIFORMITY OF DOSAGE UNITS 〈905〉: Meet the
requirements
IMPURITIES
• ORGANIC IMPURITIES
Mobile phase, Diluent, Zidovudine related compound
C standard stock solution, Standard stock solution,
Standard solution, Sample stock solution, Sample so-
lution, Chromatographic system, and System suitabil-
ity: Proceed as directed in the Assay.
USP Monographs
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of zidovudine related com-
pound C in the portion of Capsules 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 3.0%
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight, light-resistant
containers.
• USP REFERENCE STANDARDS 〈11〉
USP Zidovudine RS
USP Zidovudine Related Compound C RS
Thymine.
C5H6N2O2 126.12
.
Zidovudine Injection
DEFINITION
Zidovudine Injection is a sterile solution of Zidovudine in
Water for Injection. It contains NLT 90.0% and NMT
110.0% of the labeled amount of zidovudine
(C10H13N5O4).