title: Quantifying four-probe metabolites in a single UPLC-MS/MS run to explore the effects of cooked rhubarb on cytochrome P450 isozymes.
abstract: BACKGROUND
  Cytochrome P450 (CYP) enzymes primarily account for the oxidation of xenobiotics. A single run UPLC-MS/MS method was developed to simultaneously detect four metabolites from a probe cocktail to investigate four CYP isozymes. Paracetamol was detected to investigate CYP1A2, 4-hydroxytolbutamide for CYP2C6, 6-hydroxychlorzoxazone for CYP2E1 and dehydronifedipine for CYP3A1. 6-hydroxychlorzoxazone was detected in ESI-negative mode, while the other three were detected in ESI-positive mode.
  
  
  RESULTS
  The method was rapid (2.5 min) and validated to be specific, accurate and precise. It was successfully applied to evaluate the effects of cooked rhubarb on the activities of the four isozymes in rat microsomes. Cooked rhubarb inhibited the activity of CYP2C6 but induced both CYP2E1 and CYP3A1.
  
  
  CONCLUSIONS
  This convenient UPLC-MS/MS method was applicable. It could improve the efficiency of future studies estimating the influence of herbs, herbal products or drug entities on the activities of CYP1A2, CYP2C6, CYP2E1 and CYP3A1.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Meicun
authors.initials: M
authors.lastname: Yao
authors.forename: Jingwen
authors.initials: J
authors.lastname: Gao
authors.forename: George Q
authors.initials: GQ
authors.lastname: Li
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Xie
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000191:economics / Q000379:methods; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D012250:Rheum / Q000737:chemistry*; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000191:economics / Q000379:methods*; D013997:Time Factors
chemical_list: D004365:Drugs, Chinese Herbal; D020033:Protein Isoforms; D003577:Cytochrome P-450 Enzyme System