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Method development and validation for simultaneous determination of ebastine and its active metabolite carebastine in human plasma by liquid chromatography–tandem mass spectrometry and its application to a clinical pharmacokinetic study in healthy Chinese volunteers
Author(s) -
Phiri Margaret,
Li Duo,
Li Tengfei,
Ji Shunli,
Ling Tang,
Li Xianjing,
Gao Huaye,
Ding Li,
Shu Chang
Publication year - 2020
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4904
Subject(s) - chemistry , chromatography , protein precipitation , pharmacokinetics , selected reaction monitoring , metabolite , ammonium acetate , formic acid , active metabolite , tandem mass spectrometry , methanol , liquid chromatography–mass spectrometry , mass spectrometry , analyte , high performance liquid chromatography , pharmacology , medicine , biochemistry , organic chemistry
A simple LC–tandem mass spectrometry (MS/MS) method to determine ebastine and carebastine (active metabolite) in human plasma was developed and validated. Analytes and internal standards were precipitated by protein precipitation and separated on Synergi Hydro‐RP 80A column (4 μm, 50 mm × 2.0 mm; Phenomenex) by gradient elution with mobile phase A comprising 0.1% formic acid in 5 m m ammonium acetate (NH 4 Ac) and B comprising 100% methanol at a flow rate 0.4 mL/min. Ions were detected in positive multiple reaction monitoring mode, and they exhibited linearity over concentration range 0.01–8.0 and 1.00–300 ng/mL for ebastine and carebastine, respectively. A clinical pharmacokinetic study was conducted in healthy Chinese volunteers under fasting and fed conditions after a single oral administration of 10 mg ebastine. The maximum plasma concentration ( C max ), time to C max ( T max ) and elimination half‐life for ebastine were 0.679 ± 0.762 ng/mL, 1.67 ± 1.43 h and 7.86 ± 6.18 h, respectively, whereas these for carebastine were 143 ± 68.4 ng/mL, 5.00 ± 2.00 h and 17.4 ± 4.97 h, respectively under fasting conditions; the corresponding values under fed conditions were 4.13 ± 2.53 ng/mL, 3.18 ± 1.09 h and 21.6 ± 7.77 h for ebastine and 176 ± 68.4 ng/mL, 6.14 ± 2.0 h and 20.0 ± 4.97 h for carebastine.