Determination of taltirelin, a new stable thyrotropin-releasing hormone analogue, in human plasma by high-performance liquid chromatography turbo-ionspray ionization tandem mass spectrometry

A rapid, selective and sensitive assay of taltirelin, a novel thyrotropin-releasing hormone analogue, in human plasma has been developed. This method is based on a rapid sample preparation and high-performance liquid chromatography (HPLC) turbo-ionspray ionization tandem mass spectrometry (MS-MS). Analytes were purified from human plasma by SPE cartridge and separated by gradient HPLC. Turbo-ionspray ionization and MS-MS analyses were carried out by PE-Sciex API 3000 tandem mass spectrometer. Taltirelin was separated from its metabolite (acid form) on a semi-micro ODS column in methanol – 0.1% (v/v) formic acid. The selected reaction monitoring by precursor→product ion combination of m/ z 406→264, was used for determination of taltirelin. The linearity was confirmed in the concentration range of 17–4137 pg/ml in human plasma, and the precision of this assay, expressed as a relative deviation, was less than 9.8% over the entire concentration range with adequate assay accuracy. The results obtained by the HPLC-MS-MS method correlated well with those of the radioimmunoassay method reported previously. Therefore, the HPLC-MS-MS method is useful for the determination of taltirelin with sufficient selectivity and sensitivity on pharmacokinetic studies in human.