สารบัญ

 

Category Antibacterial. 

      Vancomycin Hydrochloride is the hydrochloride salt of a kind of vancomycin, a substance produced by the growth of Streptomyces orientalis (Family Streptomycetaceae), or a mixture of two or more such salts. It has a potency equivalent to not less than 900 μg of vancomycin per mg, calculated on the anhydrous basis.

Description Tan to brown, free-flowing powder; odourless.

Solubility Freely soluble in water; insoluble in ether and in chloroform.

Warning

      1. It may cause ototoxicity, nephrotoxicity, pseudomembranous colitis, neutropenia, red man syndrome (glycopeptide-induced anaphylactoid reaction), chemical peritonitis, or thrombocytopenia.

      2. It should be used with caution in patients with renal function impairment.

      3. Concomitant use with parenteral amphotericin B, aspirin or other salicylates, bacitracin, bumetanide, capreomycin, carmustine, cisplatin, cyclosporine, ethacrynic acid, furosemide, paromomycin, polymyxins or streptozocin or aminoglycosides should be avoided.

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

Precaution

      1. Audiograms, renal function determinations, white blood cell counts, urinalyses, or serum vancomycin concentration determination should be performed periodically.

      2. Close monitoring of serum vancomycin concentration is recommended in premature neonates and young infants.

Packaging and storage Vancomycin 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 parenteral grade.

Identification

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

      B. The retention time of the major peak in the chromatogram of the Test solution A corresponds to that in the chromatogram of the Resolution solution, as obtained in the Chromatographic purity.

      C. It yields the reactions characteristic of chlorides (Appendix 5.1). pH 2.5 to 4.5, in a 5.0 per cent w/v solution (Appendix 4.11).

Water Not more than 5.0 per cent w/w (Karl Fischer Method, Appendix 4.12).

Chromatographic purity Carry out the test as described in the “High-pressure Liquid Chromatography”(Appendix 3.5). 

      Triethylamine buffer Mix 4 ml of triethylamine and 2000 ml of water, and adjust with phosphoric acid to a pH of 3.2.

      Mobile phase A Prepare a mixture of 92 volumes of Triethylamine buffer, 7 volumes of acetonitrile and 1 volume of tetrahydrofuran.

      Mobile phase B Prepare a suitable mixture of 70 volumes of Triethylamine buffer, 29 volumes of acetonitrile and 1 volume of tetrahydrofuran.

      Mobile phase Use variable mixtures of Mobile phase A and Mobile phase B as directed for Chromatographic system. Make adjustments if necessary, changing the acetonitrile proportion in Mobile phase A to obtain a retention time of 7.5 to 10.5 minutes for the mainvancomycin peak.

      Resolution solution Prepare a solution of Vancomycin Hydrochloride RS in water containing 0.5 mg per ml, heat at 65º for 48 hours, and allow to cool.

      Test solution A Prepare a solution of the test substance in Mobile phase A containing 10 mg per ml.

      Test solution B Transfer 2.0 ml of Test solution A to a 50-ml volumetric flask, dilute with Mobile phase A 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 chemical bonded to porous silica or ceramic microparticle (5 μm), (b) Mobile phase at a flow rate of about 2 ml per minute, and (c) an ultraviolet photometer set at 280 nm. The chromatograph is programmed as follows.

      To determine the suitability of the chromatographic system, chromatograph the Resolution solution, and record the peak responses as directed under Procedure: the elution order is resolution compound 1, vancomycin B, and resolution compound 2. The resolution, R, between resolution compound 1 and vancomycin B is not less than 3.0; and the column efficiency, calculated from the vancomycin B peak, is not less than 1500 theoretical plates. Resolution compound 2 is eluted at between 3 and 6 minutes after the start of the period when the percentage of Mobile phase B is increasing from 0 to 100 per cent.

Procedure (Note Where baseline separation is not achieved, peak areas are defined by vertical lines extended from the valleys between peaks to the baseline. The main component peak may include a fronting shoulder, which is attributed to monodechlorovancomycin. This shoulder should not be integrated separately.) Inject separately equal volumes (about 20 μl) of Test solution A and Test solution B into the chromatograph, record the chromatograms, and measure the area responses for all of the peaks. (Note Correct any peak observed in the chromatograms obtained from Test solution A and Test solution B by subtracting the area response of any peak observed in the chromatogram of Mobile phase A at the corresponding elution time.)

      Calculation Calculate the percentage of vancomycin B in the test substance by the expression:

2500r_B/(25r_B + r_A),

in which r_B is the corrected area response of the main peak obtained in the chromatogram of Test solution B; and r_A is the sum of the corrected area responses of all the peaks, other than the main peak, in the chromatogram obtained from Test solution A: not less than 80.0 per cent of vancomycin B is found.

      Calculate the percentage of each other peak taken by the expression: 

100r_Ai/(25r_B + r_A),

in which r_Ai is the corrected area response of any individual peak, other than the main peak, obtained in the chromatogram of Test solution A: not more than 9.0 per cent of any peak other than the main peak is found.

Assay Carry out the microbiological assay of vancomycin hydrochloride according to the “Microbiological Assay of Antibiotics” (Appendix 6.10).

Other requirements Vancomycin 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 0.33 Endotoxin Unit per mg of vancomycin.

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