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 stock solution to a 100-mL volumetric flask. Dilute with Mobile phase to volume.
Sample solution:
Equivalent to 0.1 mg/mL of zidovudine in Mobile phase
Chromatographic system
Mode:
LC
Detector:
UV 240 nm
Column:
4.0-mm × 12.5-cm; packing L1
Flow rate:
1 mL/min
Injection size:
10 µL
System suitability
Sample:
Standard solution
[Note—The relative retention times for zidovudine related compound C and zidovudine are about 0.12 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 4.0 between zidovudine and zidovudine related compound C
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C10H13N5O4 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 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
[Note—On the basis of the synthetic route, perform either Procedure 1 or Procedure 2. ]
• Procedure 1
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 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 (mg/mL) |
| CU | = | = nominal concentration of zidovudine in the Sample solution (mg/mL) |
Acceptance criteria:
NMT 3.0%
• Procedure 2
Buffer:
5.44 mg/mL of sodium acetate trihydrate in water. Pass the solution through a suitable filter of 0.45-µm pore size.
Mobile phase:
Methanol, acetonitrile, glacial acetic acid, and Buffer (50:10:2:940)
Standard stock solution:
0.25 mg/mL of USP Zidovudine RS in Mobile phase. [Note—Sonicate to dissolve if necessary. ]
Standard solution:
0.002 mg/mL of USP Zidovudine RS in Mobile phase from the Standard stock solution
Impurity stock solution:
0.625 mg/mL of USP Zidovudine Related Compound C RS, 0.375 mg/mL of thymidine, 0.375 mg/mL of USP Stavudine RS, and 0.25 mg/mL of USP Zidovudine Related Compound B RS dissolved initially at 25% of final volume with methanol. Dilute with Mobile phase to final volume. [Note—Sonicate with intermittent shaking to dissolve, if necessary, and cool to room temperature before diluting to final volume. ]
Impurity solution:
0.05 mg/mL of USP Zidovudine Related Compound C RS, 0.03 mg/mL of thymidine, 0.03 mg/mL of USP Stavudine RS, and 0.02 mg/mL of USP Zidovudine Related Compound B RS in Mobile phase from the Impurity stock solution
System suitability solution:
1 mg/mL of USP Zidovudine RS, 0.005 mg/mL of USP Zidovudine Related Compound C RS, 0.003 mg/mL of thymidine, 0.003 mg/mL of USP Stavudine RS, 0.002 mg/mL of USP Zidovudine Related Compound B RS in Mobile phase from USP Zidovudine RS and the Impurity solution
Sample solution:
Equivalent to 1 mg/mL of zidovudine in Mobile phase
Chromatographic system
Mode:
LC
Detector:
UV 240 nm
Column:
4.6-mm × 10-cm; 3-µm packing L1
Column temperature:
25
Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Samples:
Standard solution and System suitability solution
[Note—The relative retention times are listed in Impurity Table 1. ]
Suitability requirements
Resolution:
NLT 1.4 between zidovudine and zidovudine related compound B, System suitability solution
Tailing factor:
NMT 2.0, Standard solution
Relative standard deviation:
NMT 5.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Oral Solution taken:
Result = (rU/rS) × (CS/CU) × 1/F × 100
| rU | = | = peak response of each impurity in the Sample solution |
| rS | = | = peak response of zidovudine in the Standard solution |
| CS | = | = concentration of USP Zidovudine RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of zidovudine in the Sample solution (mg/mL) |
| F | = | = relative response factor for each impurity (see Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 2.0%. [Note—All impurities listed in Impurity Table 1 excluding zidovudine related compound C ]
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Zidovudine related compound Ca |
0.08 | 1.9 | 3.0 |
| Zidovudine (thymidine)b | 0.14 | 1.0 | 0.30 |
| Stavudinec | 0.27 | 1.0 | 0.30 |
| Zidovudine | 1.00 | — | — |
| Zidovudine related compound Bd |
1.22 | 1.0 | 0.20 |
| Individual unspecified impurity | — | 1.0 | 0.20 |
|
a
5-Methylpyrimidine-2,4(1H,3H)-dione.
b
[1-(2-Deoxy-
 -d-ribofuranosyl)]thymine.
c
Thymidine, 2',3'-didehydro-3'-deoxy-.
d
3'-Chloro-3'-deoxythymidine.
|
|||
SPECIFIC TESTS
• Microbial Enumeration Tests 
61
and Tests for Specified Microorganisms 62:
Meets the requirements of the tests for absence of Salmonella species, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa
61 and Tests for Specified 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)
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
• Deliverable Volume 698:
Meets the requirements for oral solution packaged in multiple-unit containers
698:
Meets the requirements for oral solution packaged in multiple-unit containers
• Uniformity of Dosage Units 905:
Meets the requirements for oral solution packaged in single-unit containers
905:
Meets the requirements for oral solution packaged in single-unit containers
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers.
• Labeling:
If a test for Organic Impurities other than Procedure 1 is used, then the labeling states with which Organic Impurities test the article complies.
• USP Reference Standards 11
11
USP Stavudine RS 
') + '&img=../../images/v35300/cas-3056-17-5.gif',600,500);)
USP Zidovudine RS
') + '&img=../../images/v35300/cas-30516-87-1.gif',600,500);)
USP Zidovudine Related Compound B RS
3¢-Chloro-3¢-deoxythymidine.
C10H13ClN2O4 260.68
') + '&img=../../images/v35300/c11rs1266.gif',600,500);)
3¢-Chloro-3¢-deoxythymidine.
C10H13ClN2O4 260.68
USP Zidovudine Related Compound C RS
Thymine.
C5H6N2O2 126.12
') + '&img=../../images/v35300/c11rs1267.gif',600,500);)
Thymine.
C5H6N2O2 126.12
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Leonel M. Santos, Ph.D.
Senior Scientific Liaison 1-301-816-8168 |
(SM12010) Monographs - Small Molecules 1 |
| 61 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 62 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 5063
Pharmacopeial Forum: Volume No. 35(5) Page 1180