High Sensitivity Methods to Quantify Chloroquine and its Metabolite in Human Blood Samples Using LC–MS/MS

Abstract

Aim: Chloroquine is an antimalarial drug used in the treatment of Plasmodium vivax malaria. Three methods to quantify chloroquine and its metabolite in blood matrices were developed and validated. Methodology & results: Different high-throughput extraction techniques were used to recover the drugs from whole blood (50 μl), plasma (100 μl) and dried blood spots (15 μl as punched discs) followed by quantification with LC–MS/MS. The intra- and inter-batch precisions were below 15%, and thus meet regulatory acceptance criteria. Conclusion: The developed methods demonstrated satisfactory validation performance with high sensitivity and selectivity. The assays used simple and easy to automate extraction techniques. All methods were reliable with robust performance and demonstrated to be suitable to implement into high-throughput routine analysis of clinical pharmacokinetic samples.

Pharmacologic Treatment of Transplant Recipients Infected With SARS-CoV-2: Considerations Regarding Therapeutic Drug Monitoring and Drug–Drug Interactions

“…Analytical solutions exist for monitoring (hydroxy)chloroquine drug concentrations. [31][32][33] Regarding efficacy, interpretation of such TDM data is difficult because of the lack of data on target concentrations, timing of measurement, and drug adjustment strategy in the context of COVID-19 treatment. Avoiding toxic exposure is even more important considering the long half-life of (hydroxy) chloroquine; hence, monitoring (hydroxy)chloroquine concentrations is suggested for this purpose.…”

Novel methodology to perform incurred sample reanalysis on dried blood spot cards: Experimental data using darolutamide and filgotinib

“…Whole blood sample bioanalysis is cumbersome as compared with plasma/serum bioanalysis of samples and therefore, it is less preferred to be used as a matrix to generate relevant pharmacokinetic data in animals and humans. However, there are many drugs such as cyclosporin (Fahr, 1993), chloroquine (Kaewkhao et al, 2019) tacrolimus (Venkataramanan et al, 1995) and desidustat (ZYAN1) (Kansagra et al, 2018) whose pharmacokinetics have been derived using the whole blood matrix. One of the reasons for choosing whole blood as a matrix for the aforementioned drugs is due to the higher partitioning of the drug into red blood cells relative to plasma and therefore, in such instances, blood as opposed to plasma would likely represent as a key surrogate to define the pharmacokinetics of the drug.…”

Liquid chromatography tandem mass spectrometry method for determination of fulvestrant in rat plasma and its application to pharmacokinetic studies of a novel fulvestrant microcrystal

“…The matrix effect was investigated by comparing the peak areas of analyte/IS post‐extraction spiked samples with those from pure solution. A calculated matrix effect <85% (ion suppression) or >115% (ion enhancement) would imply that matrix effect was present (Kaewkhao et al, 2019). In this study, the matrix effect was assessed at LQC, MQC and HQC.…”