Ultrasensitive sub-pg/ml determination of tiotropium bromide in human plasma by 2D-UHPLC-MS/MS: challenges and solutions

Bioanalysis
Jingduan ChiRand G Jenkins

Abstract

To adequately support pharmacokinetic evaluations of tiotropium bromide in planned clinical studies. It was desirable to measure it with a LLOQ of sub pg/ml. A sensitive bioanalytical method for the determination of tiotropium in human plasma sample was successfully developed and validated in the range of 0.2-100 pg/ml. The method was successfully applied to support two clinical studies of over 3000 samples. The overall incurred sample reanalysis passing rate was 93.7%. The combination of a dual stage liquid-liquid extraction and a 2D ultra-HPLC greatly reduced matrix effects and increased assay sensitivity. When developing effective ultrasensitive assays, it is imperative to balance the aspects related to sensitivity with those that will ensure assay ruggedness.

References

Apr 14, 2000·American Journal of Respiratory and Critical Care Medicine·M R LittnerT J Witek
Feb 28, 2002·The European Respiratory Journal·R CasaburiT Witek
Jan 30, 2004·Journal of Clinical Pharmacology·Dietrich TürckTorsten Slowinski
Feb 14, 2004·Analytical and Bioanalytical Chemistry·Charles R Evans, James W Jorgenson
Jul 9, 2005·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Mona I ChurchwellDaniel R Doerge
Nov 28, 2006·Circulation Journal : Official Journal of the Japanese Circulation Society·Mahoto KatoMasafumi Kitakaze
Jan 24, 2007·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Erin ChambersJeffrey R Mazzeo
Nov 28, 2008·Electrophoresis·Ken-ichi OhnoAndreas Manz

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Citations

Jul 30, 2016·Clinical Drug Investigation·Jaime AlgortaJingduan Chi

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Methods Mentioned

BETA
reverse phase chromatography

Software Mentioned

Analyst

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