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A high‐performance liquid chromatographic method for determination of the niguldipine analogue DHP‐014
Author(s) -
Zhou Xiaofei,
Wang Qi,
Coburn Robert A.,
Morris Marilyn E.
Publication year - 2006
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.526
Subject(s) - chemistry , chromatography , high performance liquid chromatography , triethylamine , extraction (chemistry) , detection limit , coefficient of variation , pharmacokinetics , bioanalysis , reversed phase chromatography , pharmacology , medicine , organic chemistry
A simple and reliable reversed‐phase high‐performance liquid chromatography method was developed and validated for the determination of DHP‐014, a niguldipine analogue with potent P‐glycoprotein inhibitory and negligible calcium channel blocking properties, in rat plasma. DHP‐014 and niguldipine hydrochloride (the internal standard) were extracted from rat plasma by liquid extraction using hexane. DHP‐014 was then separated by HPLC on a C 18 column and quantified by ultraviolet detection at 238 nm. The mobile phase consisted of acetonitrile–aqueous 5 mm phosphate buffer (65:35, v[sol ]v) containing 0.4% (v[sol ]v) triethylamine adjusted to pH 7.0. The mean extraction efficiency of DHP‐014 was 109.0 ± 12.9, 97.7 ± 8.0 and 102.9 ± 7.5% for DHP‐014 concentrations of 10, 50 and 100 nm, respectively ( n = 5). The method was linear over the concentration range 2.5–200 nm with a regression coefficient of 0.998. The limit of detection of DHP‐014 in rat plasma was 1.0 nm. The intra‐ and inter‐day coefficients of variation for DHP‐014 in rat plasma were 4.7–7.9 and 6.9–9.9%, respectively. The intra‐ and inter‐day accuracy was 98.2–99.5 and 97.9–103%, respectively. The bioanalytical technique was used to determine DHP‐014 in plasma samples in a pharmacokinetic study of DHP‐014 administered to female Sprague–Dawley rats. Copyright © 2005 John Wiley & Sons, Ltd.