Estimation of ranolazine and eleven phase I metabolites in human plasma by liquid chromatography-atmospheric pressure chemical ionisation mass spectrometry with selected-ion monitoring.
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 (r2 > 0.980) for all the metabolites. Plasma concentrations indicated that three metabolites were present at levels higher than 10% of the parent compound.
Herron
W J
WJ
Department of Drug Metabolism and Pharmacokinetics, Quintiles Scotland Ltd, Riccarton, Edinburgh, UK.
Eadie
J
J
Penman
A D
AD
D000083:Acetanilides; D001274:Atmospheric Pressure; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D006900:Hydroxylation; D007477:Ions; D013058:Mass Spectrometry / Q000379:methods* / Q000706:statistics & numerical data; D010879:Piperazines / Q000097:blood*; D000069458:Ranolazine; D012044:Regression Analysis
D000083:Acetanilides; D007477:Ions; D010879:Piperazines; D000069458:Ranolazine