Abstract

A rapid sensitive and validated liquid chromatography/tandem mass spectrometry (LC-MS/MS) method is developed for determination of an antimigraine drug naratriptan (NAR) in human plasma using (alomtriptan) as internal standard (IS). a Liquid-liquid extraction with diethyl ether was used. The chromatographic separation was carried out using reversed phase C8 analytical Column (5 μm, 50 mm × 4.6 mm i.d.) with a simple isocratic mobile phase composed of methanol : 0.02 M ammonium formate (pH 3.5) (40:60 v/v) and flow rate 0.6 mLmin^-1. Detection was performed on a triple quadrupole mass spectrometer employing electrospray ionization (ESI) technique, operating in multiple reaction monitoring (MRM), with the transitions of 336.3 → 98.2 and 336.3 → 201.0 m/z for NAR and IS, respectively in the positive ion mode. The analysis was carried out within 2.4 min over a linear concentration range of 0.05-20 ngmL-1. The method was validated according to the FDA bio-analytical method validation guidance for industry. The developed LC-MS/MS method was successfully applied to a pharmacokinetic study of the studied drug after being orally administered by Egyptian healthy volunteers.

Keywords: Formigran; Naratriptan HCl; Mass spectrometry; Pharmacokinetics; Bio-analytical Validation ; Liquid-Liquid extraction; Antimigraine