Robinson P R, Jones M D, Maddock J, Rees L W
Simbec Research Limited, Merthyr Tydfil, Mid Glamorgan, U.K.
J Chromatogr. 1991 Mar 8;564(1):147-61. doi: 10.1016/0378-4347(91)80077-p.
A procedure for the simultaneous assay of clebopride and its major metabolite N-desbenzylclebopride in plasma has been developed. The method utilizes capillary gas chromatography-negative-ion chemical ionization mass spectrometry with selected-ion monitoring of characteristic ions. Employing 2-ethoxy analogues as internal standards, the benzamides were extracted from basified plasma using dichloromethane. Subsequent reaction with heptafluorobutyric anhydride produced volatile mono- and diheptafluorobutyryl derivatives of clebopride and N-desbenzylclebopride, respectively. The methane negative-ion mass spectra of these derivatives exhibited intense high-mass ions ideal for specific quantitation of low levels in biological fluids. Using this procedure the recovery of the drug and metabolite from human plasma was found to be 84.4 +/- 1.5% (n = 3) and 77.4 +/- 4.7% (n = 3), respectively, at 0.5 ng/ml. Measurement of both compounds down to 0.10 ng/ml with a coefficient of variation of less than 10.5% is described. Plasma levels are reported in four volunteers up to 24 h following oral administration of 1 mg of clebopride malate salt.
已开发出一种同时测定血浆中氯波必利及其主要代谢物N-去苄基氯波必利的方法。该方法采用毛细管气相色谱-负离子化学电离质谱法，并对特征离子进行选择离子监测。以2-乙氧基类似物作为内标，用二氯甲烷从碱化血浆中提取苯甲酰胺类化合物。随后与七氟丁酸酐反应，分别生成氯波必利和N-去苄基氯波必利的挥发性单七氟丁酰基和二七氟丁酰基衍生物。这些衍生物的甲烷负离子质谱显示出强烈的高质量离子，非常适合对生物流体中的低含量进行特异性定量。使用该方法，在0.5 ng/ml时，从人血浆中回收药物和代谢物的回收率分别为84.4±1.5%（n = 3）和77.4±4.7%（n = 3）。描述了两种化合物低至0.10 ng/ml的测定，变异系数小于10.5%。报告了4名志愿者口服1 mg苹果酸氯波必利盐后24小时内的血浆浓度。
