Determination of olopatadine, a new antiallergic agent, and its metabolites in human plasma by high-performance liquid chromatography with electrospray ionization tandem mass spectrometry.
A rapid, sensitive and specific assay method has been developed to determine plasma concentrations of olopatadine hydrochloride (A) and its metabolites, M1 (B), M2 (C) and M3 (D), using high-performance liquid chromatography with electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS). Olopatadine, its metabolites, and internal standard, KF11796 (E), were separated from plasma using solid-phase extraction (Bond Elut C18 cartridge). The eluate was dried, reconstituted and injected into the LC-ESI-MS-MS system. The calibration curves showed good linearity over the ranges 1-200 ng/ml for olopatadine and M3, and 2-100 ng/ml for M1 and M2, and the method was thoroughly validated and applied to the determination of olopatadine and its metabolites in plasma collected during Phase I clinical trials. Furthermore, the assay values were compared with those determined by the radioimmunoassay method, which has been routinely used to determine olopatadine in plasma.
Fujita
K
K
Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Magara
H
H
Kobayashi
H
H
D000328:Adult; D018926:Anti-Allergic Agents / Q000097:blood* / Q000493:pharmacokinetics; D019540:Area Under Curve; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003990:Dibenzoxepins / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D000069605:Olopatadine Hydrochloride; D012016:Reference Values; D012680:Sensitivity and Specificity
D018926:Anti-Allergic Agents; D003990:Dibenzoxepins; D000069605:Olopatadine Hydrochloride