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PENICILLIN V POTASSIUM

Phenoxymethylpenicillin Potassium

Category Antibacterial.

      Penicillin V Potassium contains not less than 85.0 per cent and not more than 91.0 per cent of C16H18N2O5 S, calculated on the anhydrous basis.

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

Solubility Soluble in 1.5 parts of water; slightly soluble in ethanol; practically insoluble in chloroform and in ether.

Contra-indication It is contra-indicated in patients who have shown hypersensitivity to any member of the penicillins or of the cephalosporins or other related allergens.

Warning

      1. Hypersensitivity reactions are the most common adverse effects noted with the penicillins. Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions may occur, regardless of the route of administration or the dose.

      2. Serious superinfections with resistant organisms, especially gram-negative bacteria (e.g., Pseudomonas, Proteus) and Candida, may occur following long-term therapy with penicillins.

      3. Massive doses of penicillins may cause hematologic abnormalities (including anemia, thrombocytopenia, leukopenia, neutropenia, and eosinophillia).

      4. Clostridium difficile colitis may develop in some patients.

      5. Concurrent use with bacteriostatic drugs (e.g., tetracyclines, chloramphenicol, etc.) is not recommended.

Precaution Periodic assessment of renal, hepatic and hematologic systems is recommended during long-term therapy.

Additional information Group A beta-hemolytic streptococcal infections should be treated for at least 10 days to prevent the development of acute rheumatic fever or acute glomerulonephritis.

Packaging and storage Penicillin V Potassium shall be kept in tightly closed containers.

Labelling The label on the container states storage condition.

Identification

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

      B. To 2 mg in a test-tube, add 1 drop of water followed by 2 ml of sulfuric acid and mix: the solution is colourless. Immerse the test-tube in a water-bath for 1 minute: the solution remains colourless.

      C. Place 2 mg in a test-tube, add 1 drop of water and 2 ml of formaldehyde-sulfuric acid TS and mix: the solution is red. Immerse the test-tube in a water-bath for 1 minute: a red-brown colour is produced.

      D. Ignite a small quantity. Dissolve the residue in water and filter. To the filtrate, add 2 ml of an 8 per cent w/v solution of sodium hydroxide: it yields the reactions characteristic of potassium salts (Appendix 5.1).

      E. The retention time of the major peak in the chromatogram obtained from Assay preparation corresponds to that in the chromatogram of Standard preparation, as obtained in the Assay.

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

pH 4.0 to 7.5, in a 3.0 per cent w/v solution (Appendix 4.11).

Specific rotation +220.0º to +235.0º, calculated on the dried basis, determined in a 1.0 per cent w/v solution (Appendix 4.8).

Loss on drying Not more than 1.5 per cent w/w after drying at 105º to constant weight (Appendix 4.15)

4-Hydroxypenicillin V Not more than 5.0 per cent w/w. Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5). Using the chromatogram of the Assay preparation obtained as directed in the Assay, calculate the percentage of 4-hydroxypenicillin V in the portion of Penicillin V Potassium taken by the formula:

100rp/rU,

in which rp is the 4-hydroxypenicillin V peak response, and rU is the sum of the 4-hydroxypenicillin V and penicillin V peak response.

Phenoxyacetic acid Not more than 0.5 per cent w/w. Carry out the determination as described in the “Highpressure Liquid Chromatography” (Appendix 3.5).

      Mobile phase Prepare a mixture of 65 volumes of water, 35 volumes of acetonitrile and 1 volume of glacial acetic acid. Make adjustments if necessary.

      Diluent Use pH 6.6 phosphate buffer.

      Standard solution Dissolve an accurately weighed quantity of phenoxyacetic acid in Diluent to obtain a solution having a known concentration of about 100 μg per ml.

      Test solution Dissolve an accurately weighed quantity of the test substance quantitatively in Diluent to obtain a solution containing 20.0 mg per ml. (Note Use this solution on the day prepared.)

      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 (3 to 10 μm), (b) Mobile phase at a flow rate of about 1 ml per minute, (c) an ultraviolet photometer set at 254 nm. Chromatograph Standard solution, and record the responses as directed under Procedure: the symmetry factor is not more than 1.5, and the relative standard deviation for replicate injections is not more than 2.0 per cent.

      Procedure (Note Use peak areas where peak responses are indicated.) Separately inject equal volumes (about 20 μl) of Standard solution and Test solution into the chromatograph, record the chromatograms, and measure the responses for the phenoxyacetic acid peaks. Calculate the percentage of phenoxyacetic acid in the portion of Penicillin V taken by the formula:

5C(rU/rS),

in which C is the concentration, in mg per ml, of phenoxyacetic acid in Standard solution, and rU and rS are the phenoxyacetic acid peak responses obtained from Test solution and Standard solution, respectively.

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

      Mobile phase Prepare a mixture of 650 volumes of water, 350 volumes of acetonitrile and 5.75 volumes of glacial acetic acid. Make adjustments if necessary.

      Resolution solution Prepare a solution in Mobile phase containing about 2.5 mg of penicillin G potassium and 2.5 mg of penicillin V potassium per ml.

      Standard preparation Dissolve an accurately weighed quantity of Penicillin V Potassium RS, in Mobile phase, to obtain a solution having a known concentration of about 2.5 mg per ml.

      Assay preparation Transfer about 125 mg of Penicillin V Potassium, accurately weighed, to a 50-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 (30 cm × 4 mm) packed with octadecylsilane chemically bonded to porous silica or ceramic microparticles, (b) Mobile phase at a flow rate of about 1.5 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 relative retention times are about 1.0 for penicillin G and 1.2 for penicillin V, the column efficiency from the penicilin V peak is not less than 1800 theoretical plates, and resolution factor between penicillin G and penicillin V peaks is not less than 3.0. Chromatograph Standard preparation, and record the peak response as directed under Procedure: the relative standard deviation for replicate injections 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, and measure the responses for the major penicillin V peaks and any 4-hydroxypenicillin V peaks. The relative retention times are 1.0 for 4-hydroxypenicillin V and 2.5 for penicillin V.

      Calculation Calculate the quantity of C16H18N2O5S, in of the Penicillin V Potassium taken, using the declared content of C16H18N2O5S in Penicillin V Potassium RS.

MONOGRAPHS • PENICILLIN V POTASSIUM
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หมายเหตุ / Note : TP II 2011 PAGE 140-141