Development and validation of a LC-MS/MS method for the analysis of ivermectin in plasma, whole blood, and dried blood spots using a fully automatic extraction system

Publication date: Available online 16 April 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Urs Duthaler, Claudia Suenderhauf, Stefan Gaugler, Beatrice Vetter, Stephan Krähenbühl, Felix HammannAbstractIvermectin is deployed in mass drug administration (MDA) campaigns to control parasitic diseases in the tropics, with billions of treatments having been administered in the last three decades. Simple blood sampling tools, like the dried blood spots (DBS) technique, are needed to monitor treatments in such challenging settings. Thus, we developed a fully automated method for the analysis of ivermectin in DBS microsamples, including a bioanalytical and clinical validation.Automated extraction was carried out using a DBS-MS 500 autosampler which was coupled to a LC–MS/MS system. DBS were extracted with 20 µL solvent and eluted on a C8 analytical column. Analysis was performed by multiple reaction monitoring in the positive mode.Automated sample extraction resulted in consistent recoveries (62.8 ± 4.3%) and matrix effects (68.0 ± 8.1%) between different donors and concentration levels. Intra- and inter-day accuracy and precision deviations were ≤15%, while samples with hematocrits from 20 to 60% could be quantified reliably. The achieved sensitivity of 1 ng/mL in DBS samples is sufficient to analyze ivermectin at the dose given (single oral administration of 12 mg) over a period of at least 72 h post treatment. Importantly, DBS sample...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research