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Category Antibacterial; antiprotozoal.

      Oxytetracycline Hydrochloride contains not less than 835 μg of C₂₂H₂₄N₂O₉ per mg, calculated on the dried basis.

Description Yellow, crystalline powder; taste, bitter; odourless; hygroscopic.

Solubility Freely soluble in water, but crystals of oxytetracycline base separate as a result of partial hydrolysis of the hydrochloride. Sparingly soluble in ethanol and in methanol, and even less soluble in absolute ethanol; insoluble in chloroform and in ether.

Stability It is hygroscopic. In solutions, it is destroyed when pH is less than 2 or more than 7.

Contra-indication; Warning; Precaution; Additional information See under Tetracycline Hydrochloride, p. 157.

Packaging and storage Oxytetracycline Hydrochloride shall be kept in tightly closed containers, protected from light.

Labelling The label on the container states parenteral or non-parenteral grade.

Identification

      A. The infrared absorption spectrum is concordant with the spectrum obtained from Oxytetracycline Hydrochloride RS (Appendix 2.1) or with the reference spectrum of Oxytetracycline Hydrochloride.

      B. 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.

      C. To 0.5 mg add 2 ml of sulfuric acid: a deep crimson colour is produced. Add 1 ml of water: the colour changes to yellow.

      D. It yields the reactions characteristic of chlorides (Appendix 5.1).

Crystallinity It is crystalline (Method I, Appendix 4.14).

pH 2.0 to 3.0, in a 10.0 per cent w/v solution (Appendix 4.11).

Loss on drying Not more than 2.0 per cent w/w after drying at 60º at a pressure not exceeding 0.7 kPa (about 5 Torr) for 3 hours (Appendix 4.15).

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

      Tetrabutylammonium hydrogensulfate solution Dissolve 1 g of tetrabutylammonium hydrogen sulfate in 100 ml of water. Adjust with 1 M sodium hydroxide to a pH of 7.5.

      Disodium edetate solution Dissolve 40 mg of disodium edetate in 100 ml of water. Adjust with 1 M sodium hydroxide to a pH of 7.5.

      Phosphate buffer pH 7.5 Prepare a mixture of 85 volumes of 0.33 M dipotassium hydrogenphosphate and 15 volumes of 0.33 M sodium dihydrogenphosphate. Adjust, if necessary, by adding more of the appropriate component to a pH of 7.5.

      Mobile phase Transfer, with the aid of 200 ml of water, 50 g of 2-methyl-2-propanol to a 1000-ml volumetric flask. Add 60 ml of Phosphate buffer pH 7.5, 50 ml of Tetrabutylammonium hydrogensulfate solution, and 10 ml of Disodium edetate solution, and dilute with water to volume. Make adjustments if necessary.

      Standard preparation Dissolve an accurately weighed quantity of Oxytetracycline RS in 0.01 M hydrochloric acid to obtain a solution having a known concentration of about 220 μg per ml.

      System suitability preparation Dissolve a suitable quantity of tetracycline hydrochloride in 0.01 M hydrochloric acid to obtain a solution containing about 200 μg per ml. To 3.0 ml of this solution add 1.5 ml of Standard preparation, and dilute with water to 25.0 ml.

      Assay preparation Transfer about 44 mg of Oxytetracycline Hydrochloride, accurately weighed, to a 200-ml volumetric flask, add 25 ml of 0.01 M hydrochloric acid, swirl to dissolve, dilute with 0.01 M hydrochloric acid to volume, and mix.

      Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with rigid spherical styrene-divinylbenzene copolymer maintained at 60º±2º, (b) Mobile phase at a flow rate of about 1 ml per minute and (c) an ultraviolet photometer set at 254 nm.

      To determine the suitability of the chromatographic system, chromatograph System suitability preparation, and record the peak responses as directed under Procedure: the relative retention times are about 0.6 for oxytetracycline and 1.0 for tetracycline, and the resolution factor between the oxytetracycline and tetracycline peaks is not less than 5. Chromatograph Standard preparation, and record the peak responses as directed under Procedure: the symmetry factor is not more than 1.25 and the relative standard deviation for replicate injections is not more than 1.0 per cent.

      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 C₂₂H₂₄N₂O₉ in the Oxytetracycline Hydrochloride taken, using the declared content of C₂₂H₂₄N₂O₉ in Oxytetracycline Hydrochloride RS.