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Category Antibacterial (antituberculosis). 

      Pyrazinamide Tablets contain not less than 93.0 per cent and not more than 107.0 per cent of the labelled amount of C₅H₅N₃O.

Strength available 500 mg.

Dose In combination with other antituberculosis drugs, 15 to 30 mg per kg of body weight once a day, or 50 to 70 mg per kg of body weight two or three times a week, depending on the treatment regimen. The maximum total dose should not exceed 2 g when taken daily, 3 g per dose for the three times a week regimen or 4 g per dose for the twice a week regimen.

Contra-indication; Warning; Precaution See under Pyrazinamide, p. 144.

Additional information The usual dose of pyrazinamide for patients with concomitant HIV infection is 20 to 30 mg per kg of body weight per day for the first two months of therapy.

Packaging and storage Pyrazinamide Tablets shall be protected from light.

Identification

      A. Shake a portion of the powdered tablets, containing 250 mg of pyrazinamide, with 20 ml of absolute ethanol, filter, evaporate the filtrate to dryness, and dry the residue at 105º for 30 minutes: the infrared absorption spectrum of the residue is concordant with the spectrum obtained from Pyrazinamide RS (Appendix 2.1) or with the reference spectrum of Pyrazinamide.

      B. Shake a portion of the powdered tablets, containing 50 mg of pyrazinamide, with 50 ml of water and filter. Dilute 1 ml of the filtrate to 100 ml with water: the ultraviolet absorption spectrum of the resulting solution, when observed between 230 to 350 nm, exhibits two maxima, at 268 nm and 310 nm (Appendix 2.2).

      C. Boil a portion of the powdered tablets, containing 20 mg of pyrazinamide, with 5 ml of 5 M sodium hydroxide: ammonia, recognizable by its odour, is evolved.

      D. The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.

Dissolution Carry out the test as described in the “Dissolution Test” (Appendix 4.24).

      Dissolution medium: water; 900 ml.

      Apparatus 2: 50 rpm.

      Time: 45 minutes.

      Procedure Determine the amount of C₅H₅N₃O dissolved from absorbances at the maximum at about 268 nm of filtered portions of the test solution, suitably diluted with Dissolution medium, if necessary, in comparison with a standard solution having a known concentration of Pyrazinamide RS in the same medium (Appendix 2.2).

      Tolerances Not less than 75 per cent (Q) of the labelled amount of C₅H₅N₃O is dissolved in 45 minutes.

Assay Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).

      Mobile phase Mix 10 ml of acetonitrile with 1000 ml of phosphate buffer pH 8.0. Make adjustments if necessary.

      Standard preparation Transfer an accurately weighed quantity of Pyrazinamide RS to a suitable volumetric flask, dissolve in water, sonicating to dissolve, dilute with water to volume, and mix to obtain a solution having a known concentration of about 100 μg per ml. Transfer 20.0 ml of the solution to a 50-ml volumetric flask, dilute with water to volume, and mix.

      System suitability solution Transfer 1 ml of hydrochloric acid to a 5-ml volumetric flask, dilute with Standard preparation to volume, and mix. Keep this solution on a water-bath for 5 minutes, and cool.

      Assay preparation Weigh and finely powder not less than 20 Pyrazinamide Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 100 mg of pyrazinamide, to a 500-ml volumetric flask, add 300 ml of water, and sonicate for 10 minutes. Dilute with water to volume, and mix. Filter a portion of this solution, discarding the first few ml of the filtrate. Transfer 20.0 ml of this filtrate to a 100-ml volumetric flask, dilute with water to volume, and mix.

      Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (15 cm × 3.9 mm) packed with octadecylsilane chemically bonded to totally porous silica particles, (b) Mobile phase at a flow rate of about 1 ml per minute, and (c) an ultraviolet photometer set at 270 nm.

      To determine the suitability of the chromatographic system, chromatograph Standard preparation and record the peak responses as directed under Procedure: the symmetry factor for the pyrazinamide peak is not more than 1.3. Chromatograph System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.0 for pyrazinoic acid and 2.2 for pyrazinamide, and the resolution factor between pyrazinamide and the pyrazinoic acid peaks is not less than 6.0.

      Procedure Separately inject equal volumes (about 20 μl) of Standard preparation and Assay preparation into the chromatograph, record the chromatograms and measure the responses for the major peaks.

      Calculation Calculate the content of C₅N₅N₃O in the portion of the Tablets taken, using the declared content of C₅N₅N₃O in Pyrazinamide RS.

Other requirement Comply with the requirements described under “Tablets” (Appendix 1.16).