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A volumetric absorptive microsampling LC-MS/MS method for five immunosuppressants and their hematocrit effects.
Bioanalysis 2019; 11(6):495-508B

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.

Authors+Show Affiliations

Department of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Bioanalytical Laboratory, PRA Health Sciences, Amerikaweg 18, 9407 TK, Assen, The Netherlands.Department of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Bioanalytical Laboratory, PRA Health Sciences, Amerikaweg 18, 9407 TK, Assen, The Netherlands.Department of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Department of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Department of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Department of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Department of Pharmacy, Section Pharmacokinetics, Toxicology & Targeting, University of Groningen, Groningen, The Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30892068

Citation

Koster, Remco A., et al. "A Volumetric Absorptive Microsampling LC-MS/MS Method for Five Immunosuppressants and Their Hematocrit Effects." Bioanalysis, vol. 11, no. 6, 2019, pp. 495-508.
Koster RA, Niemeijer P, Veenhof H, et al. A volumetric absorptive microsampling LC-MS/MS method for five immunosuppressants and their hematocrit effects. Bioanalysis. 2019;11(6):495-508.
Koster, R. A., Niemeijer, P., Veenhof, H., Hateren, K. V., Alffenaar, J. C., & Touw, D. J. (2019). A volumetric absorptive microsampling LC-MS/MS method for five immunosuppressants and their hematocrit effects. Bioanalysis, 11(6), pp. 495-508. doi:10.4155/bio-2018-0312.
Koster RA, et al. A Volumetric Absorptive Microsampling LC-MS/MS Method for Five Immunosuppressants and Their Hematocrit Effects. Bioanalysis. 2019;11(6):495-508. PubMed PMID: 30892068.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A volumetric absorptive microsampling LC-MS/MS method for five immunosuppressants and their hematocrit effects. AU - Koster,Remco A, AU - Niemeijer,Pascal, AU - Veenhof,Herman, AU - Hateren,Kai van, AU - Alffenaar,Jan-Willem C, AU - Touw,Daan J, Y1 - 2019/03/20/ PY - 2019/3/21/pubmed PY - 2019/7/19/medline PY - 2019/3/21/entrez KW - Mitra KW - VAMS KW - dried blood spots KW - hematocrit KW - immunosuppressants KW - microsampling KW - validation SP - 495 EP - 508 JF - Bioanalysis JO - Bioanalysis VL - 11 IS - 6 N2 - 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. SN - 1757-6199 UR - https://www.unboundmedicine.com/medline/citation/30892068/A_volumetric_absorptive_microsampling_LC_MS/MS_method_for_five_immunosuppressants_and_their_hematocrit_effects_ L2 - https://www.future-science.com/doi/full/10.4155/bio-2018-0312?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -