Characterization of a technique for rapid pharmacokinetic studies of multiple co-eluting compounds by LC/MS/MS.
A method for rapid pharmacokinetic screening of multiple potential drug candidates has been developed. This technique, based on the ability of liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) to independently monitor multiple components, enables the quantification of substances which may or may not be chromatographically resolved. Our results indicate that the limit of quantitation and accuracy of this multiple-compound LC/MS/MRM quantitation method are comparable to a single-compound LC/MS/MRM quantitation method. No apparent ion suppression due to the existence of extraneous compounds in the analytical solution and biological matrix effect are observed in the range of the calibration curve. The issue of potential residual molecule cross-talk interference existing in the multiple-reaction monitoring mode has been discussed. This multiple-compound LC/MS/MRM quantitation method can be used for high throughput pharmacokinetic screening and to assay mixtures that have co-eluting analytes or similar m/z of precursor/product ion pairs.
Tong
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X
Molecular Design and Diversity, Merck & Co., Inc., Rahway, NJ 07065, USA.
Ita
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IE
Wang
J
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Pivnichny
J V
JV
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D008297:Male; D013058:Mass Spectrometry; D010599:Pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley