Overview of therapeutic drug monitoring of immunosuppressive drugs: Analytical and clinical practices

Considerable advances in point-of-care testing (POCT) devices stem from innovations in cellphone (CP)-based technologies, paper-based assays (PBAs), lab-on-a-chip (LOC) platforms, novel assay formats, and strategies for long-term reagent storage. Various commercial CP platforms have emerged to provide cost-effective mobile health care and personalized medicine. Such assay formats, as well as low-cost PBAs and LOC-based assays, are paving the way to robust, automated, simplified, and cost-effective POCT. Strategies have also been devised to stabilize reagent storage and usage at ambient temperature. Nevertheless, successful commercialization and widespread implementation of such clinically viable technologies remain subject to several challenges and pending issues.

High-performance liquid chromatography coupled by an electrospray ion source to a tandem mass spectrometer (HPLC-ESI-MS/MS) is the current analytical method of choice for quantitation of analytes in biological matrices. With HPLC-ESI-MS/MS having the characteristics of high selectivity, sensitivity, and throughput, this technology is being increasingly used in the clinical laboratory. An important issue to be addressed in method development, validation, and routine use of HPLC-ESI-MS/MS is matrix effects. Matrix effects are the alteration of ionization efficiency by the presence of coeluting substances. These effects are unseen in the chromatogram but have deleterious impact on methods accuracy and sensitivity. The two common ways to assess matrix effects are either by the postextraction addition method or the postcolumn infusion method. To remove or minimize matrix effects, modification to the sample extraction methodology and improved chromatographic separation must be performed. These two parameters are linked together and form the basis of developing a successful and robust quantitative HPLC-ESI-MS/MS method. Due to the heterogenous nature of the population being studied, the variability of a method must be assessed in samples taken from a variety of subjects. In this paper, the major aspects of matrix effects are discussed with an approach to address matrix effects during method validation proposed.