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OBJECTIVE:To provide reference for improving the homogeneity and stability of domestic cefetamet pivoxil hydro-chloride oral solid preparation and its control standrads. METHODS:105 batches of cefetamet pivoxil hydrochloride preparations (tablets,granules,dry suspensions and dispersible tablets)were tested by statutory inspection test in respects of property,identifi-cation,weight difference or load difference,moisture,microbiological limits,related substances,dissolution degree and content, etc.,and results were analyzed. Exploratory research was conducted for its impurity sources,dissolution consistency evaluation, the correlation between the remaining validity period with relative substance and content,etc. RESULTS:Statutory tests showed, 103 batches were qualified in the 105 batches of samples(98.1%). The unqualified items were property and related substances,the other items met relevant regulations. Besides,the determination method for related substances in dispersed tablets was quite differ-ent with other preparations. Results of exploratory research showed the related substances in preparations originated from raw materi-als,degradation reaction in manufacturing or storage. Compared with domestic reference tablets and granules,f2 of dissolution of other products were mostly less than 50;there was no correlation in related substances,content with the remaining validity period. CONCLUSIONS:The 105 batches of domestic oral solid preparation of cefetamet pivoxil hydrochloride are basically qualified;cur-rent standard is basically feasible for tablets,granules and dry suspensions,while the standard for dispersible tablets needed to be improved immediately.
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Objective:To establish an HPLC method to determine the content and related substances of cefetamet pivoxil hydro-chloride tablets. Methods:A Hypersil ODS2 C18 (250 mm × 4. 6 mm,5 μm) column was used. The mobile phase was 0. 005 mol· L-1 tetrabutylammonium hydroxide solution-acetonitrile (64: 36, adjusting pH to 4. 5 with phosphoric acid). The flow rate was 1. 0 ml·min-1 . The detection wavelength was 232 nm. The column temperature was 30℃ and the injection volume was 10 μl. Results:Cefetamet was completely separated from the related substances. The equation of linear regression was Y=2.29 ×104X-4.30 ×104(r=0. 999 9) and the linear range of cefetamet was 51. 01-510. 07 μg·ml-1 . The average recovery was 99. 60% and RSD was 0. 84%(n=9). Conclusion:The method is simple, accurate and suitable. It can be used for the determination of content and related sub-stances of cefetamet pivoxil hydrochloride tablets.
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Objective To study the effect of cefetamet hydrochloride injection on the activity of 3 kinds of cytochrome P450 (CYP450) isoforms (CYP1A2, CYP3A4 and CYP2E1) in rat liver microsomes. Methods The SD rats were randomly divided into two groups: control group and cefetamet hydrochloride (CH) group, with each group containing 3 male rats and 3 female rats. The CH group was injected with cefetamet hydrochloride into the tail vein at 50 mg/(kg • d), twice a day for 7 days. A HPLC method was used for simultaneous determination of the production of metabolites and the degradation of the prototype probe substrates of 3 kinds of CYP450 isoforms, so as to evaluate the activity of hepatic CYP450. The analytical column was Diamonsil C18 column (150 mm X 4. 6 mm, 5 Fm), with the flow rate being 1. 0 mL/min. The mobile phase consisted of methanol (0. 1% formic acid) (A)-water (0. 1% formic acid)(B), 0-5 min; 18%A, 5-10 min; 18%-60%A, 10-15 min: 60%A and detected at 247 nm for determination of CYP1A2 activities; methanol (A)-water (0. 02% formic acid)(B), 0-11 min: 40%-60%A and detected at 223 nm for determination of CYP3A4 activities; and methanol (A)-water, 0-10 min: 37%-75%A and detected at 287 nm for determination of CYP2E1 activities. Results Probe substrates and their metabolites showed good linearity within the determining range (r≥0. 999 7). The precision of the method was 0. 05). Conclusion CH injection can significantly induce hepatic microsome CYP3A4 expression in SD rats, but has no induction or inhibition effect on CYP1A2 and CYP2E1, indicating that potential drug-drug interaction might occur when CH injection is coadministered with drugs metabolized by CYP3A4.
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OBJECTIVE:A RP-HPLC method was developed for determination of cefetamet in serum METHODS:The serum samples were detected on a hypersil BDS C18 column after preciptating protein with methyl alcohol and being centrifuged at a speed of 10 000 r/min The mobile phase was methyl alcohol-water=28∶72(V/V),pH=2 8,the flow rate was 1 0ml/min and the detection wavelength 262nm RESULTS:The methods showed good linearity in a concentration range of 0 53～13 25?g/ml The minimun detactable concentration of cefetamet in serum was 0 25?g/ml,the mean recovery was 100 84%,the within-day RSD was less than 4 42% and the between-day RSD was less than 4 17% CONCLUSION:The method is simple,sensitive and accurate,and may be applied to the pharmacokinetics study of cefetamet in vivo
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0.05),however,the average cost in combined group was significantly lower than in single group(P