Action and use
Nucleoside reverse transcriptase inhibitor; antiviral (HIV).
DEFINITION
Zidovudine Capsules contain Zidovudine.
The capsules comply with the requirements stated under Capsules and with the following requirements.
Content of zidovudine, C10H13N5O4
92.5 to 107.5% of the stated amount.
IDENTIFICATION
Shake a quantity of the contents of the capsules containing 0.2 g of Zidovudine with 50 mL of methanol, filter and evaporate the filtrate to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of zidovudine (RS 447).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 2 and rotate the paddle at 50 revolutions per minute.
(b) Use 900 mL of water, at a temperature of 37°, as the medium.
PROCEDURE
After 45 minutes, withdraw a 10-mL sample of the medium and filter. Measure the absorbance of the filtered medium, diluted if necessary with water, at the maximum at 266 nm using water in the reference cell, Appendix II B. Calculate the total content of zidovudine,C10H13N5O4, in the medium from the absorbance obtained from a 0.0017% w/v solution of zidovudine BPCRS in water and using the declared content of C10H13N5O4 in zidovudine BPCRS.
LIMITS
The amount of zidovudine released is not less than 75% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions protected from light.
(1) Shake a quantity of the contents of the capsules containing 0.3 g of Zidovudine with 5 mL of water in a 100 mL volumetric flask, add 30 mL of methanol, mix with the aid of ultrasound for 10 minutes, dilute to 100 mL with water and filter. Dilute 2 volumes of the filtrate to 5 volumes with water.
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase. (3) Dilute 1 volume of solution (2) to 5 volumes with the mobile phase.
(4) 0.01% w/v of zidovudine impurity standard BPCRS in the mobile phase.
(5) 0.0036% w/v of thymine in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Spherisorb ODS2 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 265 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
20 volumes of methanol and 80 volumes of water.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (4): the chromatogram closely resembles the reference chromatogram supplied with zidovudine impurity standard BPCRS; the resolution between the peaks due to zidovudine and impurity B is at least 1.5.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity C (thymine) is not greater than the area of the principal peak in the chromatogram obtained with solution (5) (3.0%);
the area of any peak corresponding to impurity B is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.0%);
the area of any peak corresponding to impurity G (retention relative to zidovudine about 2.8) is not greater than 0.5 times
the area of the peak due to zidovudine in the chromatogram obtained with solution (2) (0.5%);
the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.2%);
the sum of the areas of all the secondary peaks is not greater than 4 times the area of the principal peak in the chromatogram obtained with solution (2) (4.0%).
Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution (3) (0.1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions protected from light.
(1) Shake a quantity of the mixed contents of 20 capsules containing 0.1 g of Zidovudine with 40 mL of methanol in a 200 mL volumetric flask, shake for 30 minutes, dilute to 200 mL with water and filter. Dilute 2 volumes to 5 volumes with the mobile phase.
(2) 0.02% w/v of zidovudine BPCRS in the mobile phase.
(3) 0.01% w/v of zidovudine impurity standard BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between zidovudine and impurity B is at least 1.5.
DETERMINATION OF CONTENT
Calculate the content of C10H13N5O4 in the capsules from the chromatograms obtained using the declared content of C10H13N5O4 in zidovudine BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities B, C and G listed under Zidovudine.
