title: Metabolite quantitation: detector technology and MIST implications.
abstract: HPLC detector technology has advanced dramatically over the past 20 years, with a range of highly sensitive and specific detectors becoming available. What is still missing from the bioanalyst's armoury, however, is a highly sensitive detector that gives an equimolar response independent of the compound. This would allow for quantification of compounds without the requirement for a synthetic standard or a radiolabeled analogue. In particular, such a detector applied to metabolism studies would establish the relative significance of the various metabolic routes. The recently issued US FDA guidelines on metabolites in safety testing (MIST) focus on the relative quantitation of human metabolites being obtained as soon as feasible in the drug-development process. In this article, current detector technology is reviewed with respect to its potential for quantitation without authentic standards or a radiolabel and put in the context of the MIST guidelines. The potential for future developments are explored.
authors.affiliation: Pfizer Global Research and Development, Sandwich Laboratories, Kent, CT13 9NJ, UK. pat.wright@pfizer.com
authors.forename: Pat
authors.initials: P
authors.lastname: Wright
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Miao
authors.forename: Barclay
authors.initials: B
authors.lastname: Shilliday
mesh_terms: D002138:Calibration; D002623:Chemistry Techniques, Analytical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D055808:Drug Discovery / Q000331:legislation & jurisprudence / Q000379:methods*; D017408:Guidelines as Topic; D006801:Humans; D057230:Limit of Detection; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D004364:Pharmaceutical Preparations