Simultaneous determination of ciclesonide and its active metabolite desisobutyryl-ciclesonide in human plasma by LC-APCI-MS/MS: application to pharmacokinetic study in healthy Chinese volunteers.

Author(s): Su MX, Song M, Zhuang Y, Wang YQ, Hang TJ

Affiliation(s): Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, People's Republic of China.

Publication date & source: 2011-04-28, J Pharm Biomed Anal., 55(1):230-5. Epub 2011 Jan 19.

Publication type: Clinical Trial, Phase I; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; Validation Studies

A sensitive and highly selective liquid chromatography tandem mass spectrometric (LC/MS/MS) method was developed and validated for the determination of ciclesonide (CIC) and its active metabolite, desisobutyryl-ciclesonide (des-CIC), in human plasma. Plasma samples were extracted using methyl tert-butyl ether with mifepristone as an internal standard (IS). Separation was carried out on a C(18) column using a mixture of 0.1% formic acid solution and methanol as the mobile phase with linear gradient elution. The detection was operated with positive atmospheric pressure chemical ionization (APCI) by selective multiple reaction monitoring (SRM). The chief benefit of the present method was the high sensitivity, with the lower limit of quantification (LLOQ) as low as 10pg/mL and the linearity ranging from 10 to 10,000pg/mL for both CIC and des-CIC. The method was fully validated and successfully applied to determine CIC and des-CIC simultaneously in human plasma and proved to be suitable for phase I clinical pharmacokinetic study of inhaled ciclesonide in healthy Chinese volunteers. Copyright (c) 2011 Elsevier B.V. All rights reserved.