| A selective HPLC-UV method and two sensitive and specific LC/MS/MS methods were developed to determine the cephalosporin levels in human plasma. The methods were successfully used in pharmacokinetic studies.1. Determination of cefetamet in human plasma by high-performance liquid chromatographyCefetamet pivoxil is a prodrug that is rapidly de-esterified after absorption to yield its active metabolite, cefetamet. So a selective high-performance liquid chromatographic method was developed for the determination of cefetamet levels in human plasma. Sample preparation involved protein precipitation with 0.5 mol/1 perchloric acid. Cefetamet and the internal standard, urapidil, were separated on a Hypersil BDS C18 column, using a mobile phase of 0.05 mol/1 phosphate buffer-acetonitrile-0.05 mol/1 phosphoric acid (80: 16: 4, v/v) at a flow-rate of 1.2 ml/min. The lower limit of quantification was 0.2 g/ml. The method was applicated to study the pharmacokinetics of 20 healthy volunteers after oral administration of 500 mg of cefetamet pivoxil. Mean peak plasma levels (Cmax) of 6.78 2.12 /ml and rmax of 3.5 0.95 h were observed. The mean t\a value of 2.70 0.55 h was obtained, AUC0-t was calculated to be 40.8 12.5 g-h/ml. The method was shown sensitive in the determination of cefetamet levels in plasma samples, and was successfully used in pharmacokinetics investigation of cefetamet pivoxil.2. Determination of cefpodoxime in human plasma by liquidAbstractchromatography-tandem mass spectrometryThe prodrug cefepodoxime proxetil is the esterified form of cefpodoxime, and the parent compound can't be determined in plasma. So the objective of this investigation was to develop a sensitive and specific LC/MS/MS method for determination of cefpodoxime in human plasma and to investigate pharmacokinetics of single dose of cefpodoxime in healthy Chinese volunteers. Cefpodoxime and the internal standard cefetamet were deproteinated by acetonitrile, then separated on a Zorbax XDB-C8 column. The mobile phase consisted of acetonitrile-water-formic acid (70: 30: 1, v/v), at a flow-rate of 0.5 ml/min. A Finnigan TSQ tandem mass spectrometer equipped with ESI source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor - product ion combinations of m/z 428 - m/z 241 and m/z 398 - m/z 241 was used to quantify cefpodoxime and internal standard, respectively. The linear calibration curve was obtained in the concentration range of 0.5-8.0 g/ml. The limit of quantification was 0.5 g/ml. Each plasma sample was chromatographed within 3.0 min. The method was successfully used in the pharmacokinetic study for cefpodoxime proxetil. The main parameters obtained after an oral dose of 200 mg cefpodoxime proxetil to 18 Chinese volunteers were as follows: Cmin was found to be 2.75 0.65 (ig/ml, Tmax observed was 2.6 0.81 h , the value of t1/2 was 2.27 0.46 h, AUC0-t obtained was 15.6 3.5 g-h/ml. The method is proved to be specificity, speed, sensitivity and suitable for clinical investigation of cefpodoxime proxetil pharmacokinetics.3. Determination of cefixime in human plasma by liquid chromatography-tandem mass spectrometryA liquid chromato graphic-tandem mass spectrometric method was developed for the analysis of cefixime in human plasma. The analyte andAbstractprecipitation of plasma proteins. The compounds were eluted isocratically on a Zobarx Extend-Cis column. LC/MS/MS in positive mode used pairs of ions at m/z of 454/285 for cefixime and 398/241 for the IS (cefetamet), respectively. The linear calibration curve of cefixime was over the range of 0.025 to 8.0 ng/ml with a lower limit of quantitation of 0.025 |ag/ml. The pharmacokinetics was investigated in 18 healthy volunteers after single dose 200 mg of cefixime. Cmax value was found to be 2.73 0.79 g/ml, Tmax was 4.44 0.86 h, plasma concentration declined with mean terminal half live (tin) of 4.10 0.34 h, the value of AUC0-t was obser...
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