Quantitative determination of tiopronin in human plasma by LC‐MS/MS without derivatization

Abstract

Tiopronin (TP) is a synthetic thiol compound without chromophore. By optimizing the chromatographic conditions and sample preparation processes, an improved LC-MS/MS analytical method without derivatization has been developed and validated to determine TP concentrations in human plasma. After reduction with 1,4-dithiothreitol, plasma samples were deproteinized with 10% perchloric acid. The post-treatment samples were analyzed on a C₈ column interfaced with a triple quadrupole tandem mass spectrometer in negative electrospray ionization mode. Methanol-5 mmol/L ammonium acetate (20:80, v/v) was used as the isocratic mobile phase. The assay was linear over the concentration range of 40.0-5000 ng/mL. The intra- and inter-day precisions were within 12.9% in terms of relative standard deviation and the accuracy within 5.6% in terms of relative error. This simple and sensitive LC-MS/MS method with short analytical time (3.5 min each sample) was successfully applied to the pharmacokinetic study of TP in healthy Chinese male volunteers after an oral dose of 300 mg TP.

New quantification method for monitoring 18 l‐amino acids levels in schizophrenic patients by high‐performance liquid chromatography coupled to tandem quadrupole mass spectrometer

“…However, it requires a particular type of synthesis, which makes it expensive and time‐consuming. In numerous cases, compounds that are analogs to the analytes are utilized as an IS (Attia et al, 2016; Honour, 2011; Kaddah et al, 2021; Sharaf El‐Din et al, 2016; Yuan et al, 2012). In this study, cefalexin, cefaclor and cefadroxil were selected as ISs.…”

Determination and structural characterization of ravidasvir metabolites by LC coupled to triple quadrupole linear ion trap MS: Application to pharmacokinetics and phase I metabolism in rats

“…However, these types of internal standards are not easily obtained because they are costly and not commercially available for many compounds. In many cases, structurally related compounds to the analytes may have to be used as an IS (Attia et al, 2016; Honour, 2011; Sharaf El‐Din et al, 2016; Yuan et al, 2012). In this study, simeprevir was selected as the IS as it has approximately the same physicochemical properties as ravidasvir, where both are lipophilic with log P = 4.69 and 5.4, respectively.…”

Determination of tiopronin content in drug by copper(I)-cuproine spectrophotometry

“…In comparison to literature reports [3][4][5][6][7][8][9][10], the proposed method does not need complicated or expensive instrument, and the procedure of proposed method is simple and convenient.…”

“…Therefore, the determination of tiopronin content is of great importance. Up to now, spectrophotometry [1][2], kinetic spectrophotometry [3][4], flow injection [5][6], chemiluminescence [7], electrochemiluminescence [8], LC-MS/MS [9] and LC-ESI-MS [10] have been used to determinate the content of TPN. In these literature, spectrophotometry is a commonly used method owing to its simplicity, rapidity and cheap instrument.…”

“…In these literature, spectrophotometry is a commonly used method owing to its simplicity, rapidity and cheap instrument. In the literatures [3][4][5][6][7][8][9][10], complicated or expensive instruments are required, so the use of these methods is limited. The hydrosulfuryl(-SH) in tiopronin can quantitatively reduce Cu 2+ to Cu + , Cu + react with cuproine to form copper(І)cuproine amaranth complex in the condition of pH=5.0.…”