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Development, validation and clinical application of a LC-MS/MS method for the simultaneous quantification of hydroxychloroquine and its active metabolites in human whole blood

2014; Elsevier BV; Volume: 100; Linguagem: Inglês

10.1016/j.jpba.2014.07.009

1873-264X

Marion Soichot, Bruno Mégarbane, Pascal Houzé, L Chevillard, Julien Fonsart, Frédéric J. Baud, Olivier Laprévôte, E. Bourgogne,

Malaria Research and Control

A rapid, sensitive and specific method using liquid chromatography coupled to tandem mass spectrometry was developed for the simultaneous quantification of hydroxychloroquine (HCQ) and its three major metabolites in human whole blood. The assay, using a sample volume of 100 μL, was linear in a dynamic 25–2000 ng/mL range (R2 > 0.99) for all four compounds and suitable for the determination of elevated HCQ concentrations up to 20,000 ng/mL, after appropriate sample dilution. Inter- and intra-assay precisions were <18.2% and accuracies were between 84% and 113% for any analyte. No matrix effects were observed. The assay was successfully applied to a blood sample obtained from one poisoned patient following a massive HCQ self-ingestion resulting in an estimated concentration of 19,500 ng/mL on hospital admission. In this patient, HCQ metabolites were identified and quantified at 1123, 465 and 91 ng/mL for monodesethylhydroxychloroquine, desethylchloroquine and bisdesethylchloroquine, respectively. Further investigations are still required to assess the usefulness of the simultaneous measurement of blood concentrations of HCQ and its three active metabolites for monitoring HCQ treatment and managing HCQ poisoning.