Evaluation of peripheral blood microsampling techniques in combination with liquid chromatography-high resolution mass spectrometry for the determination of drug pharmacokinetics in clinical studies.
New bioanalytical assays were developed, validated, and applied in a clinical study for quantitative measurement of acetaminophen concentrations in blood and plasma samples. Furthermore, after validation, the bioanalytical assays were used for determination of pharmacokinetics within a group of six healthy male human volunteers after admission of a single oral dose of 500 mg of acetaminophen. Quantitative analyses were done by means of liquid chromatography-high resolution mass spectrometry and blood samples were collected at various sampling time points using different peripheral blood microsampling techniques. Post-dose peripheral collected blood samples were applied for the preparation of dry blood spots, dried matrix on paper discs, and peripheral plasma. Pharmacokinetic parameters determined were clearance (Cl), area under the curve (AUC), volume of distribution (Vd ), peak concentration (Cmax ), time of occurrence of peak concentration (Tmax ) and half-life time (T½ ). Observed pharmacokinetic values were not statistically (ANOVA) different compared to in literature reported values based on venous blood collection. The present pilot study demonstrated the feasibility of peripheral blood microsampling techniques in combination with quantitative liquid chromatography-high resolution mass spectrometry analysis for the determination of pharmacokinetics in clinical studies.
['Rincón|Juan P|JP|', 'Meesters|Roland J W|RJ|']
D000082:Acetaminophen D018712:Analgesics, Non-Narcotic D000704:Analysis of Variance D019540:Area Under Curve D001800:Blood Specimen Collection D002853:Chromatography, Liquid D005240:Feasibility Studies D006207:Half-Life D006801:Humans D008297:Male D013058:Mass Spectrometry D010865:Pilot Projects D013997:Time Factors D014018:Tissue Distribution
pharmacokinetics Acetaminophen dried blood spots dried matrix on paper discs high resolution mass spectrometry