ESTIMATION OF RANOLAZINE AND 11 PHASE-I METABOLITES IN HUMAN PLASMA BY LIQUID-CHROMATOGRAPHY ATMOSPHERIC-PRESSURE CHEMICAL-IONIZATION MASS-SPECTROMETRY WITH SELECTED-ION MONITORING

被引:34
作者
HERRON, WJ [1 ]
EADIE, J [1 ]
PENMAN, AD [1 ]
机构
[1] SYNTEX RES CTR,EDINBURGH EH14 4AP,MIDLOTHIAN,SCOTLAND
关键词
D O I
10.1016/0021-9673(95)00475-3
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The estimation of ranolazine, a novel piperazine derivative, and eleven of its Phase I metabolites has been undertaken by liquid chromatography-atmospheric pressure chemical ionisation mass spectrometry (LC-APCI-MS). Plasma samples, taken on day 5 of a multiple-dose study, were extracted by solid-phase extraction (SPE) and analysed, using a gradient HPLC system coupled to the APCI source of a Finnigan MAT TSQ 700 mass spectrometer. Metabolites were analysed in selected-ion monitoring (SIM) mode, using an instrument control language (ICL) procedure. The LC-MS combination allowed resolution of all eleven metabolites, including four hydroxylated metabolites and five unresolved components. The results from the linear regression showed good correlation (r(2) > 0.980) for all the metabolites. Plasma concentrations indicated that three metabolites were present at levels higher than 10% of the parent compound.
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页码:55 / 60
页数:6
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