LAUSR

&NA; 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 C18 columns. A simple isocratic separation mode was used with a mobile phase consisted of acetonitrile and 10 mM phosphate buffer adjusted to pH 3.0 (20:80; v/v) at flow rate 1.0 mL min−1. 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 15–2000 ng mL−1 with detection limits of 4.8‐ 6.2 ng mL−1 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. Graphical abstract Figure. No caption available. HighlightsAn efficient, fast, and selective Zirconia‐PBD‐HPLC method is developed and validated for plasma determination of triptans.Zirconia‐PBD provides a mixed ion‐exchange and reversed phase separation mechanism.Inclusion of the extremely stable zirconia particles with cross‐linked PBD polymer provides high chemical and thermal stability.Zirconia‐PBD column was a superior alternative to C18 columns in terms of selectivity, peak symmetry and analysis speed.The developed method was applied to study in a pharmacokinetic study of zolmitriptan in rats.