Fast and Efficient Zirconia-based Reversed Phase Chromatography for Selective Determination of Triptans in Rat Plasma

Selective and fast chromatographic method was essential for the determination of triptans, selective serotonin receptor (5-HT1) agonists, in biological specimens. However, selective chromatographic separation of these highly basic drugs is a challenging problem on silica-based stationary phases. Zirconia-based stationary phases have been introduced as an efficient alternative for silica-based columns offering unique stability, selectivity, and retention ability for various classes of drugs. Herein, a new selective, fast and reproducible high performance liquid chromatographic method (HPLC) was developed and validated for the determination of four triptans in plasma samples namely; Sumatriptan (SMT), Zolmitriptan (ZLT), Eletriptan (ELT) and Rizatriptan (RZT). Zirconia-based polybutadiene (PBD) column was used for the separation and quantitation of the studied triptans in rat plasma based on mixed mode ion exchange and reversed phase chromatography. Zirconia-PBD column (ZirChrom-PBD) has enhanced chemical and thermal stability, selectivity and provides high resolution for the investigated triptans in short analysis time compared with the commonly used C columns. A simple isocratic separation mode was used with a mobile phase consisted of acetonitrile and 10mM phosphate buffer adjusted to pH 3.0 (20:80; v/v) at flow rate 1.0mLmin. The column was maintained at 50°C and effluent was monitored by photodiode array detector (PDA). The developed method was validated in agreement with US-FDA guidelines and was appropriate for analysis of triptans in plasma samples. The linearity range obtained for the developed HPLC method was 15-2000ngmL with detection limits of 4.8- 6.2ngmL for all the studied triptans. The developed zirchonia-PBD-HPLC method was applied successfully to study the pharmacokinetics of ZLT in rats after a single oral dose. The method was proved to be valuable for therapeutic drug monitoring and bioavailability studies of the studied triptans.