| High-performance liquid chromatography methods coupled with ultraviolet detection (HPLC-UV) and with mass spectrometry (LC/MS~ or LCIMSIMS) were the main choices in the studies of drug metabolism and pharmacokinetics. Several rapid, sensitive and specific methods using these hyphenated, techniques were developed for qualitative and. quantitative analysis of meloxicain, trimebutine and cisapride in biosaniples. The characteristics of the techniques above in the research of drug metabolism and pharmacokinetics were discussed. 1. HIPLC-UV method for analysis of meloxicam in human plasma; and pharmacokinetics of meloxicam in Chinese volunteers A simple, specific and sensitive HPLC-UV method was established to determine meloxicam in human plasma. Meloxicam and the internal standard, piroxicam, were isolated from acidified plasma using liquid-liquid extraction and analyzed on a Cis reversed phase column with UV detection at 361 nm. The limit of quantification was 20.0 ng/mL and assay accuracy within ?2%. Intra-day and inter-day precisions were within 8%. After validation procedures, the method was used to study the pharmacokinetic behavior of meloxicam after an oral dose of 15 mg meloxicam to 20 healthy male volunteers. There were individual differences significantly in the pharmacokinetics of meloxicani, and the 20 volunteers were classified into extensive metabolizers and poor metabolizers according to the AUCo~ values. The main pharrnacokinetic parameters of extensive and poor metabolizers were obtained as follows: C,~ were 1528.0 ?194.1 and 1916.7 ?408.4 ng/mL; t,,2 were 20.80 ?3.59 and 38.25 ?9.20 h; AUCo~ were 48.94 ?10.12 and 109.82 ?8.23 ~&gb/mL; CIJF were 5.23 ?1.15 Abstract 4 and 2.28?. l6mUmin, respectively. It was suggested that the difference of elimination for meloxicani was a key factor to influence the pharmacokinetic profile of the unchanged drug. The pbarmacokinetic data showed that the clinical dosage regimen of meloxicam should be individualized. 2. LCJMS~ method for identification of metabolites of meloxicam in human urine The main metabolites of meloxicam in human urine were isolated and detected by LCtMS~ method, and the feature of the hyphenated technique was discussed. The urine samples were treated by solid phase extraction before analysis. A microbial transformation combined with semi-preparution HPLC method was adopted to gain the reference substance of 5?hydroxymethyl metabolite, whose structure was elucidated by NMR. Compared with the HPLC retention time and mass spectrum of the reference compound, a total of 3 metabolites were identified in human urine. These include 5?hydroxymethyl meloxicam, 5?carboxyl meloxicam and 2-(N-methyl)-amino-sulfonyl benzoic acid. The results appended the reported metabolism of meloxicam. It was shown that the LC/MS~ technique had potent ability of structural speculation and high specificity in the study of drug metabolism. 3. LC/MS/MS method for determination of trimebutine and cisapride in mixed plasma samples, and its application in pharmacokinetic studies A LCIMS/MS method was developed for the detection of tri... |
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