Remco A Koster1,2, Pascal Niemeijer1,2, Herman Veenhof1, Kai van Hateren1, Jan-Willem C Alffenaar1, Daan J Touw1,3. 1. Department of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 2. Bioanalytical Laboratory, PRA Health Sciences, Amerikaweg 18, 9407 TK, Assen, The Netherlands. 3. Department of Pharmacy, Section Pharmacokinetics, Toxicology & Targeting, University of Groningen, Groningen, The Netherlands.
Abstract
Aim: The aim of this study was to develop and validate a LC-MS/MS assay for tacrolimus, sirolimus, everolimus, cyclosporin A and mycophenolic acid using volumetric absorptive microsampling tips as a sampling device and to investigate the effect on the recoveries of the analyte concentration in combination with the hematocrit (HT), which included temsirolimus (a structural analog). Results: The maximum observed overall bias was 9.6% for the sirolimus LLOQ, while the maximum overall coefficient of variation was 8.3% for the everolimus LLOQ. All five immunosuppressants demonstrated to be stable in the volumetic absorbtive microsampling tips for at least 14 days at 25°C. Biases caused by HT effects were within 15% for all immunosuppressants between HT levels of 0.20 and 0.60 l/l, except for cyclosporin A, which was valid between 0.27 and 0.60 l/l. Reduced recoveries were observed at high analyte concentrations in combination with low HT values for sirolimus, everolimus and temsirolimus. Conclusion: A robust extraction and analysis method in volumetric absorptive microsampling tips was developed and fully validated. HT- and concentration-related recovery effects were observed but were within requirements of the purpose of the analytical method.
Aim: The aim of this study was to develop and validate a LC-MS/MS assay for tacrolimus, sirolimus, everolimus, cyclosporin A and mycophenolic acid using volumetric absorptive microsampling tips as a sampling device and to investigate the effect on the recoveries of the analyte concentration in combination with the hematocrit (HT), which included temsirolimus (a structural analog). Results: The maximum observed overall bias was 9.6% for the sirolimus LLOQ, while the maximum overall coefficient of variation was 8.3% for the everolimus LLOQ. All five immunosuppressants demonstrated to be stable in the volumetic absorbtive microsampling tips for at least 14 days at 25°C. Biases caused by HT effects were within 15% for all immunosuppressants between HT levels of 0.20 and 0.60 l/l, except for cyclosporin A, which was valid between 0.27 and 0.60 l/l. Reduced recoveries were observed at high analyte concentrations in combination with low HT values for sirolimus, everolimus and temsirolimus. Conclusion: A robust extraction and analysis method in volumetric absorptive microsampling tips was developed and fully validated. HT- and concentration-related recovery effects were observed but were within requirements of the purpose of the analytical method.
Authors: O W Akkerman; R Duarte; S Tiberi; H S Schaaf; C Lange; J W C Alffenaar; J Denholm; A C C Carvalho; M S Bolhuis; S Borisov; J Bruchfeld; A M Cabibbe; J A Caminero; I Carvalho; J Chakaya; R Centis; M P Dalcomo; L D Ambrosio; M Dedicoat; K Dheda; K E Dooley; J Furin; J-M García-García; N A H van Hest; B C de Jong; X Kurhasani; A G Märtson; S Mpagama; M Munoz Torrico; E Nunes; C W M Ong; D J Palmero; R Ruslami; A M I Saktiawati; C Semuto; D R Silva; R Singla; I Solovic; S Srivastava; J E M de Steenwinkel; A Story; M G G Sturkenboom; M Tadolini; Z F Udwadia; A R Verhage; J P Zellweger; G B Migliori Journal: Int J Tuberc Lung Dis Date: 2022-07-01 Impact factor: 3.427
Authors: Nasrullah Undre; Imran Hussain; John Meijer; Johannes Stanta; Gordon Swan; Ian Dawson Journal: Ther Drug Monit Date: 2021-06-01 Impact factor: 3.681