Quantitative determination of saroglitazar, a predominantly PPAR alpha agonist, in human plasma by a LC–MS/MS method utilizing electrospray ionization in a positive mode

Abstract

A sensitive LC-MS/MS method was developed and validated for quantitation of saroglitazar using turboion spray interface with positive ion mode. A liquid-liquid extraction, with a mixture of dichloromethane and diethyl ether, was employed for the extraction of saroglitazar and glimepiride (IS) from human plasma. The chromatographic separation was achieved using an ACE-5, C (4.6 × 100 mm) column with a gradient mobile phase comprising acetonitrile and ammonium acetate buffer with trifluoracetic acid in purified water. Both analytes were separated within 10 min with retention times of 4.52 and 2.57 min for saroglitazar and IS, respectively. Saroglitazar quantitation was achieved by the summation of two MRM transition pairs (m/z 440.2 to m/z 366.0 and m/z 440.2 to m/z 183.1), while that of IS was achieved using transition pair m/z 491.3 to m/z 352.0. The calibration standards of saroglitazar showed linearity from 0.2 to 500 ng/mL, with a lower limit of quantitation of 0.2 ng/mL. The biases for inter- and intra-batch assays were -7.51-1.15% and -11.21 to -3.25%, respectively, while the corresponding precisions were 5.04-8.06% and 1.53-7.68%, respectively. The developed method was used to monitor the plasma concentrations of saroglitazar in clinical samples.

Liver inflammation and fibrosis

“…Thus, PPARs are possible therapeutic targets in NASH (Figure 1). In fact, PPAR agonists have been reported and are now in clinical trials for the treatment of NASH (124,125). FXR signaling is also a potential target because it facilitates secretion of bile acids (126), resulting in decreased hepatic storage of triglycerides and fatty acid esters (Figure 1).…”

Technologies to improve the sensitivity of existing chromatographic methods used for bioanalytical studies

“…They believed that the selection of the stable transition ion pairs is important; however, matrix effect could be neglectable after validating that it is not impact the bias of quantification. More recently, this approach was successfully applied to an LC–MS/MS method for quantification of saroglitazar in human plasma, using which the authors obtained an LLOQ of 0.2 ng/mL for saroglitazar and good linearity from 0.2 to 500 ng/mL (Ghoghari et al, ). In another study, Li, Li, and Kellermann () achieved a threefold to fourfold increase in the sensitivity of catecholamines using MRM summation, which allowed simultaneous quantification of the trace level of catecholamines in human peripheral blood mononuclear cells.…”

“…It is worth however, matrix effect could be neglectable after validating that it is not impact the bias of quantification. More recently, this approach was successfully applied to an LC-MS/MS method for quantification of saroglitazar in human plasma, using which the authors obtained an LLOQ of 0.2 ng/mL for saroglitazar and good linearity from 0.2 to 500 ng/mL (Ghoghari et al, 2016). In another study, Li, Li, and Kellermann (2016)…”