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AMPICILLIN SODIUM

Category Antibacterial.

          Ampicillin Sodium contains not less than 87.0 per cent and not more than 100.5 per cent of C16H19N3O4S, calculated on the anhydrous basis.

Description White to off-white, crystalline powder.

Solubility Soluble in 2 parts of water and in 50 parts of acetone; slightly soluble in chloroform; insoluble in ether, in liquid paraffin and in fixed oils.

Stability It is hygroscopic.

Contra-indication; Warning; Precaution; Additional information See under Penicillin V Potassium, p. 140.

Warning It should be given with caution to patients with infectious mononucleosis since they are susceptible to ampicillin-induced skin rashes.
          See also under Penicillin V Potassium, p. 140.

Packaging and storage Ampicillin Sodium shall be kept in tightly closed containers and stored at a temperature not exceeding 25º. If it is intended for parenteral administration, 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 Ampicillin Sodium RS (Appendix 2.1) or with the reference spectrum of Ampicillin Sodium.
          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. It yields the reactions characteristic of sodium salts (Appendix 5.1).

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

pH 8.0 to 10.0, in a 1.0 per cent w/v solution (Appendix 4.11).

Specific rotation +258º to +287º, calculated on the anhydrous basis. Dissolve 62.5 mg in a 0.4 per cent w/v solution of potassium hydrogenphthalate and dilute to 25.0 ml with the same solvent (Appendix 4.8).

Water Not more than 2.0 per cent w/w (Karl Fischer Method, Appendix 4.12).

Heavy metals Not more than 20 ppm (Method II, Appendix 5.2). Use 2.0 g; for the standard preparation, use lead standard solution (2 ppm Pb).

N,N-Dimethylaniline Not more than 20 ppm (Appendix 5.16).

Limit of dichloromethane Not more than 0.2 per cent w/w. Carry out the determination as described in the “Gas Chromatography” (Appendix 3.4).
          Internal standard solution Prepare a solution of dioxane in dimethyl sulfoxide containing about 2.1 mg per ml.

          Standard solution Dissolve an accurately weighed quantity of dichloromethane in Internal standard solution to obtain a solution having a known concentration of about 330 μg per ml.
          Test solution Dissolve about 500 mg of Ampicillin Sodium, accurately weighed, in 3.0 ml of Internal standard solution.
          Chromatographic system The chromatographic procedure may be carried out using (a) a glass column (1.8 m × 4 mm) packed with a 10 per cent w/w polyethylene glycol (average molecular weight about 1500) on
silanized diatomaceous support, maintained at 65º, (b) the injection port and the detector block maintained at 100º and 260º, respectively, (c) nitrogen as the carrier gas at a flow rate of about 60 ml per minute, and (d) a flame ionization detector. Chromatograph Standard solution, and record the peak responses as directed under Procedure: the relative retention times are about 0.5 for dichloromethane and 1.0 for dioxane, the resolution
factor between the dichloromethane peak and the dioxane peak is not less than 4, and the relative standard deviation for replicate injections is not more than 5 per cent.
          Procedure Separately inject equal volumes (about 1 μl) of Standard solution and Test solution into the chromatograph, record the chromatograms, and measure the responses for the dichloromethane and dioxane peaks. Calculate the percentage of dichloromethane in Ampicillin Sodium.

Assay Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).
          Diluent Mix 10 ml of 1 M potassium dihydrogenphosphate and 1 ml of 1 M acetic acid, dilute with water to 1000 ml, and mix.
          Resolution solution Dissolve caffeine in Standard preparation to obtain a solution containing about 120 μg per ml.
          Mobile phase Prepare a suitable mixture of 909 volumes of water, 80 volumes of acetonitile 10 volumes of 1 M potassium dihydrogenphosphate and 1 volume of 1 M acetic acid. Make adjustments if necessary.
          Standard preparation Dissolve a suitable quantity of Ampicillin RS, accurately weighed, in Diluent to obtain a solution having a known concentration of about 1 mg per ml, using shaking and sonication, if necessary, to achieve complete dissolution. Use this solution promptly after preparation.
          Assay preparation (Note Ampicillin Sodium is hygroscopic. Minimize exposure to the atmosphere, and weigh promptly.) Transfer an accurately weighed quantity of Ampicillin Sodium, containing about 100 mg of anhydrous ampicillin, to a 100-ml volumetric flask, dissolve in and dilute with Diluent to volume, and mix. Use this solution promptly after preparation.
          Chromatographic system The chromatographic procedure may be carried out using (a) a stainless steel column (30 cm × 4 mm) and a pre-column (5 cm × 4 mm) packed with octadecylsilane chemically bonded to porous silica or ceramic microparticles (5 to 10 μm), (b) Mobile phase at a flow rate of about 2 ml per minute, and (c) an ultraviolet photometer set at 254 nm.
          To determine the suitability of the chromatographic system, chromatograph Resolution solution and record the peak responses as directed under Procedure: the resolution factor between the caffeine and the ampicillin
peaks is not less than 2.0 and the relative retention times are about 0.5 for ampicilin and 1.0 for caffeine. Chromatograph Standard preparation, and record the peak responses as directed under Procedure: the relative standard deviation for replicate injections is not more than 2.0 per cent and the symmetry factor for the amoxicillin peak is not more than 1.4.
          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 C16H19N3O4S using the declared content of C16H19N3O4S in Ampicillin RS.

Other requirements Ampicillin Sodium 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 0.15 Endotoxin Unit per mg of ampicillin.
          Sterility Complies with the “Sterility Test” (Method I, Appendix 10.1).

 

MONOGRAPHS • AMPICILLIN SODIUM
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หมายเหตุ / Note : TP II 2011 PAGE 28 - 30