Determination of benidipine hydrochloride in human plasma by capillary column gas chromatography-negative ion chemical ionization mass spectrometry.
A highly sensitive and specific determination method of a new calcium antagonist, benidipine hydrochloride, in human plasma has been developed using capillary column gas chromatography with negative ion chemical ionization mass spectrometry. A deuterated analogue of benidipine hydrochloride was used as an internal standard. Benidipine hydrochloride was extracted from plasma with diethyl ether under basic conditions, back-extracted with 0.5 M sulphuric acid, and reextracted with diethyl ether under basic conditions. For gas chromatography, a solventless injection port was used, and the whole extract was injected. Fragment ions at m/z 488 (benidipine) and m/z 493 (internal standard) were used as monitoring ions for selected-ion monitoring. The detection limit was 0.02 ng/ml with 0.5 ml of plasma. The coefficient of variation of intra-day assay was 17.4% and 12.1% at the 0.02 and 0.1 ng/ml levels, respectively. This method has made it possible to detect the plasma level of unchanged drug up to 12 h after an 8-mg oral dose of benidipine hydrochloride to humans.
Magara
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Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Kobayashi
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Kobayashi
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D000328:Adult; D002121:Calcium Channel Blockers / Q000097:blood* / Q000493:pharmacokinetics; D004095:Dihydropyridines / Q000097:blood* / Q000493:pharmacokinetics; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D007477:Ions; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007477:Ions; C061004:benidipine