Development and validation of a simple and rapid UHPLC-MS/MS method for the quantification of hydroxychloroquine in plasma and blood samples in the emergency context of SARS-CoV-2 pandemic.

Therapeutic drug monitoring (TDM) of hydroxychloroquine has been recommended to optimize the treatment of COVID-19 patients. The authors describe an ultra-high-performance liquid chromatography tandem spectrometry ( UHPLC-MS/MS) method developed in a context of emergency, to analyze hydroxychloroquine (HCQ) in both human plasma and blood samples.After adding the labeled internal standard and simple protein precipitation, plasma samples were analyzed using a C18 column. Blood samples required evaporation before analysis. The total chromatographic run time was 4 min (including 1.5 min of column equilibration). The assay was linear over the calibration range (r > 0.99) and up to 1.50 µg/mL for the plasma samples (5.00 µg/ml for the blood matrix). The limit of quantification was 0.0150 µg/mL for plasma samples (0.05 µg/ml blood matrix) with accuracy and precision ranging from 91.1 % to 112 % and from 0.750 % to 11.1 %, respectively. Intra- and inter-day precision and accuracy values were within 15.0 %. No significant matrix effect was observed in the plasma or blood samples. This method was successfully applied to patients treated for COVID-19 infection. A simple and rapid UHPLC-MS/MS method adapted to HCQ TDM in the context of SARS-CoV-2 infection was successfully developed and validated.