Determination of Taspoglutide in Human and Animal Plasma Using Liquid Chromatography-Tandem Mass Spectrometry with Orthogonal Column-Switching

作者：Heinig Katja^*; Wirz Thomas

来源：Analytical Chemistry, 2009, 81(10): 3705-3713.

DOI：10.1021/ac900422e

A highly sensitive liquid chromatographic method with online solid-phase extraction (SPE) and tandem mass spectrometric detection was developed for the quantification of the synthetic peptide drug taspoglutide in human and animal plasma. Sample preparation consisted of simple protein precipitation or automated off-line SPE using mixed mode cation exchange material, optionally preceded by cleavage of potential antidrug antibody complexes. Excellent selectivity was obtained by a novel orthogonal column switching approach, employing hydrophilic interaction liquid chromatography (HILIC) for online SPE followed by chromatographic separation on a 300 A pore size C18 column. The use of a stable isotope labeled drug (C-terminal arginine containing six (13)C and four (15)N atoms) as internal standard improved the quality and ruggedness of the method. The lower limits of quantitation (LLOQ) in human and animal plasma were 10.0 and 50.0 pg/mL, respectively, extracting only 250 or 100 mu L sample aliquots. Precisions and accuracies were below 15% CV and between 89% and 114%, respectively. The method was successfully employed to analyze samples from pharmacokinetic studies.

• 出版日期2009-5-15