High-performance liquid chromatographic determination of tazobactam and piperacillin in human plasma and urine.

A high-performance liquid chromatographic (HPLC) method with ultraviolet (UV) absorbance was developed for the analysis of piperacillin-tazobactam (tazocillin), in plasma and urine. The detection was performed at 218 nm for tazobactam and 222 nm for piperacillin. The procedure for assay of these two compounds in plasma and of piperacillin in urine involves the addition of an internal standard (ceftazidime for tazobactam and benzylpenicillin for piperacillin) followed by a treatment of the samples with acetonitrile and chloroform. To quantify tazobactam in urine, diluted samples were analysed using a column-switching technique without internal standard. The HPLC column, LiChrosorb RP-select B, was equilibrated with an eluent mixture composed of acetonitrile-ammonium acetate (pH 5). The proposed technique is reproducible, selective, and reliable. The method has been validated, and stability tests under various conditions have been performed. Linear detector responses were observed for the calibration curve standards in the ranges 5-60 micrograms/ml for tazobactam, and 1-100 micrograms/ml for piperacillin and spans what is currently though to be the clinically relevant range for tazocillin concentrations in body fluids. The limit of quantification was 3 micrograms/ml for tazobactam and 0.5 microgram/ml for piperacillin in plasma and urine. Extraction recoveries from plasma proved to be more than 85%. Precision, expressed as C.V., was in the range 0.4-18%.

High-performance liquid chromatographic determination of cis-dichlorodiammineplatinum(II) in plasma ultrafiltrate.

A reproducible, simple and sensitive high-performance liquid chromatographic method was described for the quantitative analysis of cis-diamminedichloroplatinum(II) (CDDP) in ultrafiltrate plasma in the presence of nickel chloride as internal standard. CDDP and the internal standard were chelated by exchange with diethyldithiocarbamate. After derivatization, the mixture was directly injected into the column. Chromatography was performed on an Ultrasphere column and the eluent measured spectrophotometrically at 260 nm for CDDP and at 250 nm for the internal standard. The peak area ratio of CDDP to the internal standard varied linearly with concentration over the range 0.05-10 micrograms ml-1. Precision and reproducibility were both excellent and the limit of quantification was 0.03 micrograms ml-1 using only 0.5 ml of ultrafiltrate. The present method, without extraction, should be entirely automated. This assay may be suitable for therapeutic drug monitoring in patients receiving CDDP.

Bayesian estimation of p-aminohippurate clearance by a limited sampling strategy.

This study describes a methodology to calculated p-aminohippurate (PAH) clearance (CL) and volume of distribution (V) with both the population parameters and one or two samples taken during the disposition and the elimination phase after a single intravenous infusion. The computer program P-PHARM was used, and a log-normal distribution and a heteroscedastic residual error distribution were assumed. Ninety-six patients with and without renal insufficiency were available for analysis, and a two-compartment model was used for data modeling. Population parameters were evaluated for 70 patients (mean number of observed concentration per individual, 6) by a three-step approach. In step 1, the computer program was used to estimate the average pharmacokinetic parameters without taking into account the demographic and/or biological factors. In step 2, the relationship between the posterior individual estimates and the covariables was investigated with multiple linear stepwise algorithm. In step 3, the population parameters were re-estimated considering the relationship with the covariables. From the regression performed in step 2, the following covariables were included: serum creatinine, body surface area, and body weight. The population averages of CL and V were 30.7 +/- 2.36 L/h and 10.6 +/- 1.29 L, respectively. To evaluate the predictive performance of the population parameters, the remaining 26 patients were used. The population parameters combined with one or two individual PAH plasma concentrations led to a bayesian estimation of individual CL and V. This estimation was compared with the classical procedure of parameter estimation (individual fitting from multiple blood samples).(ABSTRACT TRUNCATED AT 250 WORDS)