Determination Of Tiopronin Research Articles

Capillary Electrophoresis Determination of Tiopronin in Human Urine After Derivatization with 2-chloro-1-methylquinolinium Tetrafluoroborate

Capillary Electrophoresis Determination of Tiopronin in Human Urine After Derivatization with 2-chloro-1-methylquinolinium Tetrafluoroborate

Spectrophotometric Determination of Tiopronin in Pharmaceutical Samples by Phosphorus Molybdenum Blue

Spectrophotometric Determination of Tiopronin in Pharmaceutical Samples by Phosphorus Molybdenum Blue

Determination of Tiopronin in Human Plasma and Pharmacokinetics by LC-ESI-MS

A rapid, sensitive and specific method based on high performance liquid chromatography-electrospray ionization-mass spectrometry was developed for the determination of tiopronin in human plasma. In this study, vitamin C and dithiothreitol were used as the reducer and to release and stabilize tiopronin from dimeric mixed forms with endogenous thiols encountered during pretreatment of plasma samples. The separation was successfully achieved on an Agilent SB-Aq column packed with 5 μm C18 silica, using an aqueous formic acid solution (pH 4.5–4.7), 0.5 mM tris(hydroxymethyl)aminomethane and methanol (95:5, v/v) as the mobile phase. Mass spectra were acquired in selective ion monitoring mode, using the [M − H] − ions of tiopronin at m/z 162.0 and the [M − H]− of the internal standard sodium cyclamate at m/z 178.0, respectively. This quantitative assay was fully validated with respect to precision, repeatability and accuracy. The correlation coefficients were >0.9995 in the range 0.025–8.15 μg mL−1 in human plasma. The mean recoveries were above 85%. The limit of quantitation was 0.012 μg mL−1 with a relative standard deviation of inter-day and intra-day accuracy of less than 15%. This LC-ESI-MS method was also successfully applied to a pharmacokinetic study after oral administration of formulated tiopronin to healthy volunteers. The elimination half-life (T 1/2) was 21.5 ± 11.1 h.

Determination of Tiopronin in Human Plasma by SPE then Reversed-Phase HPLC–UV

An accurate, simple and sensitive method based on reversed-phase high-performance liquid chromatography with UV detection has been developed for determination of tiopronin (TP) in human plasma. TP in plasma was reacted with p-bromophenacyl bromide (p-BPB) to give the TP-p-BPB adduct and this derivative was then extracted from the plasma on a silica gel cartridge. Potential interfering compounds were removed by washing with water, and the TP-p-BPB adduct was then eluted with acetonitrile. The organic phase obtained was evaporated to complete dryness under a stream of nitrogen. The residue was dissolved in acetonitrile and this solution was injected on to a reversed-phase ODS HPLC column. The mobile phase was usually the ternary mixture acetonitrile–water–trifluoroacetic acid, 40:59.88:0.12 (v/v). The retention times of TP-p-BPB and the internal standard adduct were 14.4 and 17.9 min, respectively. No interfering peaks were encountered in several blank plasma samples examined. The limit of detection for TP was 12 ng mL−1. Extraction recovery exceeded 70%. The calibration plot for the TP derivative was linear in the range 40−4000 ng mL−1, regression coefficient 0.9989, and the coefficient of the variation of the points of the calibration plot was below 10%. The method was validated appropriately and successfully applied to the determination of TP in human plasma.

Chemiluminescence determination of tiopronin by flow injection analysis based on cerium (IV) oxidation sensitized by quinine.

A flow injection analysis method is proposed for the determination of tiopronin based upon the oxidation by cerium(IV) in dilute sulfuric acid medium and sensitized by quinine. With the peak height as a quantitative parameter applying optimum working conditions, tiopronin is determined over the 1–400 µM range (150 µl per injection, n = 10, r = 0.9994) with a detection limit of 0.34 µM and an RSD (n = 10) less than 2% at 20 and 50 µM. The proposed method, combining the advantages of speed and sensitivity, was applied to the routine determination of tiopronin in a pharmaceutical preparation.

Chemiluminescent determination of tiopronin and its metabolite, 2-mercaptopropionic acid, in urine by HPLC coupled with a flow injection set-up.

Chemiluminescent determination of tiopronin and its metabolite, 2-mercaptopropionic acid, in urine by HPLC coupled with a flow injection set-up.

Chemiluminescence determination of tiopronin by flow injection analysis based on cerium(IV) oxidation sensitized by quinine.

A flow injection analysis method is proposed for the determination of tiopronin based upon the oxidation by cerium(IV) in dilute sulfuric acid medium and sensitized by quinine. With the peak height as a quantitative parameter applying optimum working conditions, tiopronin is determined over the 1-400 microM range (150 microliters per injection, n = 10, r = 0.9994) with a detection limit of 0.34 microM and an RSD (n = 10) less than 2% at 20 and 50 microM. The proposed method, combining the advantages of speed and sensitivity, was applied to the routine determination of tiopronin in a pharmaceutical preparation.

Chemiluminescence determination of tiopronin and its metabolite 2-mercaptopropionic acid in human urine by HPLC coupled with flow injection

In previous pharmacokinetic studies tiopronin, a drug used for effective treatment of cystinuria and rheumatoid arthritis, and its metabolite 2-mercaptopropionic acid were analysed by conventional liquid chromatography with pre- and post-column derivatization and UV detection. Now a novel HPLC-coupled chemiluminescence-flow-injection analysis (CL-FIA) method has been developed for the determination of tiopronin and 2-mercaptopropionic acid in urine. The method is based on chemiluminescence from a Ce(IV) oxidation system sensitized by quinine, as proposed earlier by this group, and flow-injection analysis. The method, which has the advantages of high sensitivity and selectivity, simple sample treatment and prompt production of results, has also been preliminarily adapted for pharmacokinetic study of tiopronin in urine.