Simultaneous Quantification of Psychotropic Drugs in Human Plasma and Breast Milk and its Application in Therapeutic Drug Monitoring and Peripartum Treatment Optimization
Résumé
Background. Therapeutic drug monitoring (TDM) is recommended for several psychotropic drugs, particularly in sensitive situations such as the peripartum period. This study aimed to develop an ultra-high-performance liquid chromatography-tandem spectrometry method for the simultaneous quantification of 14 psychotropic drugs in human plasma and four in breast milk.
Methods. The samples were precipitated with methanol containing the stable isotopelabelled analogs. Chromatographic separation was performed using a Phenomenex Luna Omega Polar C18 column. Detection was performed using a triple-quadrupole mass spectrometer equipped with an electrospray ionization interface. The method was fully validated in plasma according to the European Guidelines on Bioanalytical Method Validation and partially validated in breast milk by determining the intra-day precision and accuracy, linearity, lower limit of quantification, and matrix effect.
Results. The correlation coefficients of the calibration curves were greater than 0.99.
Coefficients of variation ranged from 3.05-14.66 % and 0.62-14.90 % for internal standardnormalized matrix effect, 1.4-14.1 % and 2.1-10.4 % for intra-day precision, and 3.2-13.9 % and 4.1-9.6 % for inter-day precision, in plasma and milk, respectively. The relative error in accuracy did not exceed ± 15 % for any analyte. The method was successfully applied clinically to measure the concentrations of psychotropic drugs in 952 plasma samples, among which, 43 % of the concentrations were out of the therapeutic range, and 13 breast milk samples, with calculated relative infant doses ranging from 0.32-8.18%.
To the author's knowledge, this is the first routine technique validated for the quantification of psychotropic drugs in both plasma and breast milk, allowing treatment optimization and prevention of adherence issues, including those in breastfeeding patients.
Domaines
Sciences du Vivant [q-bio]Origine | Fichiers produits par l'(les) auteur(s) |
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Origine | Fichiers produits par l'(les) auteur(s) |
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Origine | Fichiers produits par l'(les) auteur(s) |
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