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Category Antibacterial.

      Lincomycin Hydrochloride has a potency equivalent to not less than 790 μg of C₁₈H₃₄N₂O₆S per mg.

Description White or almost white, crystalline powder; odourless or faint odour.

Solubility Freely soluble in water; soluble in dimethylformamide; very slightly soluble in acetone.

Contra-indication It is contra-indicated in patients with a history of hypersensitivity reactions to clindamycin.

Warning

      1. It may cause pseudomembranous colitis, gastrointestinal disturbances, hypersensitivity reactions, thrombophlebitis, erythema, or pain and swelling at the injection site.

      2. It should be used with caution in patients with a history of gastro-intestinal disease, particularly colitis, severe renal impairment, in atopic individuals or in those receiving drugs having neuromuscular blocking action.

      3. Rapid intravenous administration may cause hypotension, syncope and cardiac arrest.

      4. Due to antagonizing effect, concomitant use with chloramphenicol or erythromycin should be avoided.

      5. Risk-benefit should be considered if it is to be used in pregnant or nursing women.

Precaution

      1. If clinically important or persistent diarrhea occurs during lincomycin therapy, the drug should be discontinued.

      2. Liver and kidney function tests and blood cell counts should be performed periodically.

Packaging and storage Lincomycin Hydrochloride shall be kept in tightly closed containers, protected from light. It shall also be kept under sterile condition.

Labelling The label on the container states (1) storage condition; (2) parenteral grade.

Identification

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

      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. Dissolve about 10 mg in 2 ml of dilute hydrochloric acid and heat in a water-bath for 3 minutes. Add 3 ml of sodium carbonate TS and 1 ml of a 2 per cent w/v solution of sodium nitroferricyanide: a violet-red colour develops.

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

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

pH 3.0 to 5.5, in a 10 per cent w/v solution (Appendix 4.11).

Specific rotation +135º to +150º, calculated on the anhydrous, determined in a 4.0 per cent w/v solution (Appendix 4.8).

Water Not less than 3.0 per cent and not more than 6.0 per cent w/w (Karl Fischer Method, Appendix 4.12).

Lincomycin B Use the chromatogram obtained from Assay preparation in the Assay: the area of the lincomycin B peak is not greater than 5.0 per cent of the sum of the areas of the lincomycin B peak and the lincomycin peak.

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

      Mobile phase Add 13.5 ml of phosphoric acid  to 1000 ml of water, and adjust with strong ammonia solution  to a pH of 6.0. Prepare a mixture of 78 volumes of this solution, 15 volumes of acetonitrile, and 15 volumes of methanol. Make adjustments if necessary.

      Standard preparation Dissolve an accurately weighed quantity of Lincomycin Hydrochloride RS in Mobile phase  to obtain a solution having a knownconcentration of about 1.2 mg per ml, using sonication if necessary to effect solution.

      Assay preparation To about 12 mg of Lincomycin Hydrochloride, accurately weighed, add 10.0 ml of Mobile phase. Shake by mechanical means for 5 minutes, and sonicate if necessary to effect solution.

      Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with octylsilane chemically bonded to totally porous silica particles (3 to 10 μm), (b) Mobile phase  at a flow rate of about 1 ml per minute, and (c) an ultraviolet photometer set at 210 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 main lincomycin peak is not more than 1.3 and the relative standard deviation for replicate injections is not more than 2.0 per cent. The relative retention times are about 0.5 for lincomycin B and 1.0 for lincomycin.

      Procedure Separately inject equal volumes (about 10 μl) of Standard preparation and Assay preparation into the chromatograph, record the chromatograms and measure the responses for the major peaks.

      Calculation Calculate the potency of C₁₈H₃₄N₂O₆S in the Lincomycin Hydrochloride taken, using the declared potency of C₁₈H₃₄N₂O₆S in Lincomycin Hydrochloride RS.

Other requirements Lincomycin Hydrochloride intended for parenteral administration complies with the following additional requirements.

      Bacterial endotoxins When tested as described in the “Test for Bacterial Endotoxins” (Appendix 8.5), it contains not more than 0.5 Endotoxin Unit per mg of lincomycin.

      Sterility Complies with the “Sterility Test” (Method I, Appendix 10.1).