Showing papers by "Stig Pedersen-Bjergaard published in 2012"

On-chip electromembrane extraction for monitoring drug metabolism in real time by electrospray ionization mass spectrometry

Abstract: A temperature controlled (37 °C) metabolic reaction chamber with a volume of 1 mL was coupled directly to electrospray ionization mass spectrometry (ESI-MS) by the use of a 50 μm deep counter flow micro-chip electromembrane extraction (EME) system. The EME/ESI-MS system was used to study the in vitro metabolism of amitriptyline in real time. There was no need to stop the metabolisms by protein precipitation as in conventional metabolic studies, since the EME selectively extracted the drug and metabolites from the reaction solution comprised of rat liver microsomes in buffer. Compositional changes in the reaction chamber were continuously detected 9 seconds later in the MS. Most of this time delay was due to transport of the purified extract towards the ESI source. The EME step effectively removed the enzymatic material, buffer and salts from the reaction mixture, and prevented these species from being introduced into the ESI-MS system. The on-chip EME/ESI-MS system provided repeatability for the amitriptyline signal intensity within 3.1% relative standard deviation (RSD) (n = 6), gave a linear response for amitriptyline in the tested concentration range of 0.25 to 15 μM, and was found not to be prone to ion-suppression from major metabolites introduced simultaneously into the EME/ESI-MS system. The setup allowed the study of fast reactions kinetics. The half-life, t1/2, for the metabolism of 10 μM amitriptyline was 1.4 minutes with a 12.6% RSD (n = 6).

Introduction to pharmaceutical chemical analysis

Abstract: Introduction to Pharmaceutical Chemical Analysis , Introduction to Pharmaceutical Chemical Analysis , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

Alginate and chitosan foam combined with electromembrane extraction for dried blood spot analysis.

Abstract: Samples of 10 μL of whole blood containing citalopram, loperamide, methadone, and sertraline as model substances were spotted on alginate and chitosan foams as sampling media. After drying and storage at room temperature, the punched out dried blood spot and the foam was dissolved in 300 μL of 1 mM HCl. With alginate foam as sampling medium, the analytes dissolved completely after 3 min. Enrichment and cleanup was performed with electromembrane extraction for 10 min. The analytes were collected in 21 μL of 10 mM formic acid as the acceptor phase, and the extracts were analyzed by liquid chromatography–mass spectrometry (LC–MS). Sample preparation of blood spots on commercial cards was also performed (Whatman FTA DMPK and Agilent Bond Elut DMS) using elution procedures recommended by the manufacturers. The recoveries obtained with the commercial cards were lower for most of the model analytes compared to the recoveries obtained with alginate and chitosan foams as sampling media. The procedure used for Agil...

Liquid-phase microextraction and desorption electrospray ionization mass spectrometry for identification and quantification of basic drugs in human urine

Abstract: Hollow fibre liquid-phase microextraction (LPME) and desorption electrospray ionization mass spectrometry (DESI-MS) were evaluated for the identification and quantification of basic drugs in human urine samples. The selective extraction capabilities of three-phase LPME provided a significant reduction in the matrix effects otherwise observed in direct DESI-MS analysis of urine samples. Aqueous LPME extracts (in 10 mM HCl) were deposited on porous Teflon, dried at room temperature, and the dried spots were then analyzed directly with DESI-MS in full scan mode. Pethidine, diphenhydramine, nortriptyline, and methadone were used as model compounds for identification, and their limits of identification were determined to be 100, 25, 100, and 30 ng/mL, respectively. In a reliability test with 19 spiked urine samples, 100 % of the positive samples containing the model drugs in concentrations at or above the limit of identification were identified. Diphenhydramine was used as a model compound for quantitative analysis with diphenhydramine-d5 as an internal standard. The calibration curve was linear in the range 50–2000 ng/mL (R2 = 0.992) with a limit of quantification at approximately 140 ng/mL. The intra- and inter-day relative standard deviations were <9.5 %. In a reliability test with six spiked urine samples, deviations between the measured and the true values for diphenhydramine were in the range 0.2–22.9 %. Copyright © 2011 John Wiley & Sons, Ltd.

Hollow Fiber Liquid-Phase Microextraction

Abstract: This chapter discusses hollow fiber liquid-phase microextraction (LPME). The chapter comprises a short discussion of the basic setup and principles for LPME, and the historical development. The theory of LPME is also discussed including equations for extraction recoveries and extraction kinetics. This theory is the basis for method optimization, which is covered comprehensively in a forthcoming section. Different applications of LPME are also discussed, with special emphasis on environmental and pharmaceutical analysis. Most attention is focused on recent applications in which LPME has been combined with either gas chromatography–mass spectrometry or high-performance liquid chromatography–mass spectrometry (LC-MS). This chapter also presents a comprehensive discussion of the performance of LPME. Electromembrane extraction, which is a new type of LPME utilizing electrical fields for extraction, is also mentioned. Future perspectives are also discussed. The chapter contains 105 references to original research papers on LPME.