Chemometrics assisted liquid chromatography–mass spectrometry in full scan mode for quantification of two immunosuppressant drugs in whole blood samples

Immunosuppressant drugs are used increasingly to prevent allograft rejection in organ transplant patients. Cyclosporine A and the structurally related macrolides tacrolimus, sirolimus and everolimus are increasingly used for maintenance of immunosuppression in combination with a steroid and mycophenolic acid. All of these agents have narrow therapeutic indices and, as a result of highly variable inter-subject pharmacokinetics, require therapeutic drug monitoring to individualize dosage based on target concentration ranges [1]. In the present study, a strategy that combines three-way liquid chromatography–mass spectrometry (LC–MS) data with second-order calibration methods based on multivariate curve resolution-alternating least squares (MCR-ALS) algorithm and alternating trilinear decomposition(ATLD) algorithm were developed for simultaneous determination of two immunosuppressant drugs in human blood samples. Acceptable resolution and quantification results in the presence of matrix interferences were achieved and the second-order advantage was fully exploited. The average recoveries were between 90% and 110% with average relative standard deviation of less than 10% in both methods.Indicating that the strategy could provide satisfactory prediction results for multi-drug assay in human blood samples only using liquid chromatography -mass spectrometer in full scan mode[2]. Considering the advantages of fast, low-cost, high sensitivity, and no need of complicated chromatographic and tandem mass spectrometric conditions optimization, the proposed strategy is expected to be extended as an attractive alternative method with respect to LC-MS/MS, to quantify analyte(s) of interest in complex systems such as cells, biological fluids, food, environment, pharmaceuticals and other complex samples[3].