Determination of tolperisone in human plasma by liquid chromatography/tandem mass spectrometry for clinical application

Abstract

We have developed and validated a simple, rapid, and sensitive liquid chromatography analytical method employing tandem mass spectrometry (LC-MS/MS) for the determination of tolperisone, a centrally acting muscle relaxant, in human plasma. After liquid-liquid extraction with methyl t-butyl ether, chromatographic separation of tolperisone was performed using a reversed-phase Luna C(18) column (2.0mm×50mm, 5μm particles) with a mobile phase of 10mM ammonium formate buffer (pH 3.5) - methanol (12:88, v/v) and quantified by tandem mass detection in ESI positive ion mode. The flow rate of the mobile phase was 250μL/min and the retention times of tolperisone and the internal standard (IS, dibucaine) were both 0.6min. The calibration curves were linear over a range of 0.5-300ng/mL (r>0.999). The lower limit of quantification, using 200μL human plasma, was 0.5ng/mL. The mean accuracy and precision for intra- and inter-day validation of tolperisone were within acceptable limits. The LC-MS/MS method reported here showed improved sensitivity for quantification of tolperisone in human plasma compared with previously described analytical methods. Lastly, the validated method was successfully applied to a pharmacokinetic study in humans.

Enantioselective Separation and Simultaneous Determination of Tolperisone and Eperisone in Rat Plasma by LC‐MS/MS

“…LLOQ was determined to be 0.2 ng/mL for each enantiomer. The coefficient of determination of the four enantiomers was better than 0.9996. the lnearity range of previous reported methods for TOL was 0.5–300 ng/mL and EPI was 0.02‐20.0 ng/mL . These methods successfully demonstrated the pharmacokinetics of both drugs.…”

“…A few analytical and bioanalytical methods have been reported for the estimation of tolperisone and eperisone individually or in pharmaceutical combined dosage forms or in biological matrixes by high‐performance liquid chromatography (HPLC) using different detection methods, viz. ultraviolet (UV) and mass spectrometry (MS) . Some of the researchers have worked on gas chromatography (GC) and GC‐MS for the estimation of eperisone in human serum .…”

Multidimensional voltammetry: Four-way multivariate calibration with third-order differential pulse voltammetric data for multi-analyte quantification in the presence of uncalibrated interferences

“…Tolperisone (TOP) is a centrally acting muscle relaxant that is used for relieving spasticity of neurological origin and muscle spasms associated with painful locomotor diseases [30][31][32]. Only a few reports have been described in the literatures on the analytical methods for the simultaneous determination of TOP and LC [33]. Therefore, the development of a sensitive and selective method for the simultaneous determination of LD, CD, MD, TRA, AC, LC, and TOP is highly desirable for analytical applications and diagnostic research.…”