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Validation and clinical application of an LC-MS/MS method for the quantification of everolimus using volumetric absorptive microsampling.

Abstract

Everolimus is a mammalian target of rapamycin inhibitor approved for the treatment of various tumor types. Less invasive measurement of everolimus concentrations could facilitate pharmacokinetic studies and personalized dosing based on whole blood concentrations, known as therapeutic drug monitoring. Volumetric Absorptive Microsampling (VAMS) has been introduced as a patient friendly, less invasive sampling technique to obtain an accurate volume of whole blood regardless of hematocrit value. We describe the bioanalytical validation and clinical application of a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to quantify everolimus using VAMS. For the quantification, 13C2D4-Everolimus was used as internal standard (IS). Everolimus and the IS were extracted with methanol from the VAMS device, which was evaporated after ultrasonification and shaking. The residue was reconstituted in 20 mM ammonium formate buffer and methanol (50%, v/v) of which 5 μL was injected into the LC-MS/MS system. Quantification was performed for the ammonium adduct of everolimus in positive electrospray ion mode. The VAMS method met all pre-defined validation criteria. Accuracy and precision were within 11.1% and ≤14.6%, respectively. Samples were shown to be stable on the VAMS device for at least 362 days at ambient temperatures. Considerable biases from -20 to 31% were observed over a 30-50% hematocrit range. Although the method fulfilled all validation criteria, the perceived advantage of VAMS over dried blood spot sampling could not be demonstrated. Despite the effect of hematocrit, using an empirically derived formula the whole blood everolimus concentration could be back calculated with reasonable accuracy in the clinical application study.

Authors+Show Affiliations

Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Louwesweg 6, 1066 EC Amsterdam, the Netherlands. Electronic address: r.verheijen@nki.nl.Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Louwesweg 6, 1066 EC Amsterdam, the Netherlands.Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.Department of Medical Oncology and Clinical Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands; Department of Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Louwesweg 6, 1066 EC Amsterdam, the Netherlands.Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Louwesweg 6, 1066 EC Amsterdam, the Netherlands.Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Louwesweg 6, 1066 EC Amsterdam, the Netherlands; Department of Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.Department of Medical Oncology and Clinical Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands.Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Louwesweg 6, 1066 EC Amsterdam, the Netherlands; Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30530116

Citation

Verheijen, R B., et al. "Validation and Clinical Application of an LC-MS/MS Method for the Quantification of Everolimus Using Volumetric Absorptive Microsampling." Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, vol. 1104, 2019, pp. 234-239.
Verheijen RB, Thijssen B, Atrafi F, et al. Validation and clinical application of an LC-MS/MS method for the quantification of everolimus using volumetric absorptive microsampling. J Chromatogr B Analyt Technol Biomed Life Sci. 2019;1104:234-239.
Verheijen, R. B., Thijssen, B., Atrafi, F., Schellens, J. H. M., Rosing, H., de Vries, N., ... Huitema, A. D. R. (2019). Validation and clinical application of an LC-MS/MS method for the quantification of everolimus using volumetric absorptive microsampling. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 1104, pp. 234-239. doi:10.1016/j.jchromb.2018.11.030.
Verheijen RB, et al. Validation and Clinical Application of an LC-MS/MS Method for the Quantification of Everolimus Using Volumetric Absorptive Microsampling. J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Jan 1;1104:234-239. PubMed PMID: 30530116.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Validation and clinical application of an LC-MS/MS method for the quantification of everolimus using volumetric absorptive microsampling. AU - Verheijen,R B, AU - Thijssen,B, AU - Atrafi,F, AU - Schellens,J H M, AU - Rosing,H, AU - de Vries,N, AU - Beijnen,J H, AU - Mathijssen,R H J, AU - Steeghs,N, AU - Huitema,A D R, Y1 - 2018/11/30/ PY - 2018/08/07/received PY - 2018/11/28/revised PY - 2018/11/30/accepted PY - 2018/12/12/pubmed PY - 2019/1/30/medline PY - 2018/12/12/entrez SP - 234 EP - 239 JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JO - J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. VL - 1104 N2 - Everolimus is a mammalian target of rapamycin inhibitor approved for the treatment of various tumor types. Less invasive measurement of everolimus concentrations could facilitate pharmacokinetic studies and personalized dosing based on whole blood concentrations, known as therapeutic drug monitoring. Volumetric Absorptive Microsampling (VAMS) has been introduced as a patient friendly, less invasive sampling technique to obtain an accurate volume of whole blood regardless of hematocrit value. We describe the bioanalytical validation and clinical application of a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to quantify everolimus using VAMS. For the quantification, 13C2D4-Everolimus was used as internal standard (IS). Everolimus and the IS were extracted with methanol from the VAMS device, which was evaporated after ultrasonification and shaking. The residue was reconstituted in 20 mM ammonium formate buffer and methanol (50%, v/v) of which 5 μL was injected into the LC-MS/MS system. Quantification was performed for the ammonium adduct of everolimus in positive electrospray ion mode. The VAMS method met all pre-defined validation criteria. Accuracy and precision were within 11.1% and ≤14.6%, respectively. Samples were shown to be stable on the VAMS device for at least 362 days at ambient temperatures. Considerable biases from -20 to 31% were observed over a 30-50% hematocrit range. Although the method fulfilled all validation criteria, the perceived advantage of VAMS over dried blood spot sampling could not be demonstrated. Despite the effect of hematocrit, using an empirically derived formula the whole blood everolimus concentration could be back calculated with reasonable accuracy in the clinical application study. SN - 1873-376X UR - https://www.unboundmedicine.com/medline/citation/30530116/Validation_and_clinical_application_of_an_LC_MS/MS_method_for_the_quantification_of_everolimus_using_volumetric_absorptive_microsampling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1570-0232(18)31219-4 DB - PRIME DP - Unbound Medicine ER -