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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 [Angstrom] pore size C18 column. The use of a stable isotope labeled drug (C-terminal arginine containing six [sup.13]C and four [sup.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 [micro]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.

The analytical capabilities of liquid chromatography tandem mass spectrometry for sensitive and highly selective determination of target compounds in complex biological samples makes it well suited for high-throughput analysis. We report the fast separation of six benzodiazepines isolated from human urine via selected reaction monitoring liquid chromatography/mass spectrometry using short dwell times to accommodate fast-eluting chromatographic peaks. The analytes were extracted from human urine samples along with their deuterium-labeled internal standards by a simple liquid-liquid extraction in 96-well plates. Using four autosamplers coupled to one chromatographic column and one tandem mass spectrometer operated in the turbo ion spray mode with positive ion detection, 1152 samples (12 96-well plates) were analyzed in less than 12 h. Through an electronic switching box designed and constructed in-house, the autosamplers were synchronized with the mass spectrometer so that injections were made as soon as the mass spectrometer was ready to collect data. Each run required 30 s to complete with another 7-8 s for the data system to load the next data file to be collected. Chromatographic integrity and ion current response remained relatively constant for the duration of the analyses. The results show acceptable precision and accuracy and demonstrate the feasibility of using fast separations with tandem mass spectrometry for high-throughput analysis of biological samples containing multiple analytes.

Fatty alcohol ethoxylates (FAEs) are applied in commercial formulations (laundry detergents) as complex mixtures of alkyl and ethoxylate homologues. Therefore, efficient analytical methods are required for product control. Capillary electrophoresis, a modern analytical separation technique, was used to separate FAEs in technical products and household formulations after derivatization with phthalic anhydride. The well-established high-performance liquid chromatography was used as reference and supplementary method. UV detection after derivatization with phenyl isocyanate or light scattering detection has been carried out. Sample components have been identified by standard addition or by comparison to known products. The peak pattern can be considered as a 'fingerprint' of the product and is characteristic for a defined composition.