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Category Antibacterial.

         Clindamycin Hydrochloride is the hydrated hydrochloride salt of clindamycin, a substance produced by the chlorination of lincomycin. It has a potency equivalent to not less than 800 μg of C₁₈H₃₃ClN₂O₅S per mg.

Description White or almost white, crystalline powder.

Solubility Freely soluble in water, in dimethylformamide and in methanol; soluble in ethanol; practically insoluble in acetone.

Contra-indication It is contra-indicated in patients with a history of hypersensitivity to lincosamides or in patients with diarrheal states.

Warning
          1. It may cause severe potentially fatal Clostridium difficile-associate diarrhea and colitis.
          2. It may cause nausea, vomiting, skin rashes or urticaria, transient elevation of serum alkaline phosphatase and transaminases, jaundice, or blood dyscrasia.
          3. It should be used with extreme caution in patients with impaired hepatic and renal functions, in pregnant women, newborns or infants, or in patients who are receiving erythromycin, chloramphenicol, neuromuscular blocking agents, or antiperistaltic antidiarrheals.
          4. Risk-benefit should be considered if it is to be used in pregnant or nursing women. Precaution Complete blood counts and hepatic function determinations are required at periodic intervals during prolonged therapy. Discontinue medication and/or check with a physician immediately if signs of pseudomembranous colitis occur during or after therapy.

Additional information
          1. Since the drug does not adequately diffuse into the cerebrospinal fluid, it is not recommended for the treatment of meningitis.
          2. Cross-sensitivity between clindamycin and doxorubicin may be possible.

Packaging and storage Clindamycin Hydrochloride shall be kept in tightly closed containers and stored at a temperature not exceeding 30º.

Identification
          A. The infrared absorption spectrum is concordant with the spectrum obtained from Clindamycin Hydrochloride RS (Appendix 2.1) or with the reference spectrum of Clindamycin Hydrochloride.
          B. Dissolve 10 mg in 2 ml of dilute hydrochloric acid and heat on 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.
          C. It yields the reactions characteristic of chlorides (Appendix 5.1).

Crystallinity It is crystalline (Appendix 4.14).

pH 3.0 to 5.5, in a 10.0 per cent w/v solution (Appendix 4.11).

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

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

Sulfated ash Not more than 0.5 per cent w/w (Appendix 5.3).

Related substances Not more than 4.0 per cent w/w of 7-epiclindamycin and not more than 2.0 per cent w/w of clindamycin B; not more than 1.0 per cent w/w of any other individual related substance, and not more than 6.0 per cent w/w of the total of all related substances, including lincomycin. Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).
          Mobile phase and Chromatographic system Proceed as directed in the Assay.
          Standard solution Dissolve accurately weighed quantities of Lincomycin Hydrochloride RS and Clindamycin Hydrochloride RS quantitatively in Mobile phase to obtain a solution having known concentrations of about 0.5 mg per ml of Lincomycin Hydrochloride RS and 1 mg per ml of Clindamycin Hydrochloride RS per ml. Transfer 10.0 ml of this solution to a 100-ml volumetric flask, dilute with Mobile phase to volume, and mix.
          Test solution Transfer about 125 mg of the test substance, accurately weighed, to a 25-ml volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.
          To determine the suitability of the chromatographic system, chromatograph Standard solution, and record the peak responses as directed under Procedure: the relative retention times are about 0.4 for lincomycin, 0.65 for clindamycin B, 0.8 for 7-epiclindamycin, and 1.0 for clindamycin.
          Procedure Separately inject equal volumes (about 10 μl) of Test solution and Standard solution, and record the chromatograms for a period of time that is six times the retention time of the clindamycin peak.
          Calculations Calculate the percentage of lincomycin in the test substance taken by the expression:

2.5(C_LP_L/W)(r_U/r_S),

in which CL is the concentration, in mg per ml, of Lincomycin Hydrochloride RS in Standard solution; PL is the potency in μg of lincomycin (C₁₈H₃₄N₂O₆S) per mg, of Lincomycin Hydrochloride RS; W is the weight, in mg, of the test substance taken to prepare Test solution; and r_U and r_S are the lincomycin peak responses obtained from Test solution and Standard solution, respectively. Calculate the percentage of all other related substance in the Clindamycin Hydrochloride taken by the expression:

2.5(C_P/W)(r_i/r_C),

in which C is the concentration, in mg per ml, of Clindamycin Hydrochloride RS in Standard solution; P is the potency, in μg, of clindamycin (C₁₈H₃₃ClN₂O₅S) per mg, of Clindamycin Hydrochloride RS; W is the weight, in mg, of the test substance taken to prepare Test solution; r_i is the response of an individual related substance, other than lincomycin, in the chromatogram obtained from Test solution and r_C is the clindamycin peak response in the chromatogram obtained from Standard solution.

Assay Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).
          Mobile phase Mix 55 volumes of buffer solution prepared by dissolving 6.8 g of potassium dihydrogenphosphate in 1000 ml of water, and adjusting with 8 M potassium hydroxide to a pH of 7.5, and 45 vol-umes of acetonitrile. Make adjustments if necessary. (Note Increasing the proportion of acetonitrile in the Mobile phase decreases the retention time, and decreasing it increases the resolution between 7-epiclindamycin and clindamycin.)
          Standard preparation Dissolve an accurately weighed quantity of Clindamycin Hydrochloride RS quantitatively in Mobile phase to obtain a solution having a known concentration of about 1 mg per ml.
          Assay preparation Transfer about 125 mg of Clindamycin Hydrochloride, accurately weighed, to a 25-ml volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix. Transfer 5.0 ml of this solution to a 25-ml volumetric flask, dilute with Mobile phase 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 octadecylsilane chemically bonded to porous silica or ceramic microparticles (5 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 resolution factor between clindamycin B and 7- epiclindamycin is not less than 2.4, the resolution factor between clindamycin and 7-epiclindamycin is not less than 3.0, the symmetry factor for the clindamycin peak is not more than 1.2, and the relative standard deviation for the clindamycin peak is not more than 1.0 per cent.

         Procedure Separately inject equal volumes (about 10 μl) of Standard preparation and Assay preparation into the chromatograph, record the chromatograms for a period of time that is about twice the retention time of the clindamycin peak and measure the major peaks.

         Calculation Calculate the content, in μg, of C₁₈H₃₃ClN₂O₅S in each mg of the Clindamycin Hydrochloride taken by the expression:

125(C_P/W)(r_u/r_s),

in which C is the concentration, in mg per ml, of Clindamycin Hydrochloride RS in Standard preparation; P is the potency, in μg of clindamycin per mg, of Clindamycin Hydrochloride RS; W is the weight, in mg, of Clindamycin Hydrochloride taken to prepare Assay preparation; and ru and rs, are the clindamycin peak responses obtained from Assay preparation and Standard preparation, respectively.