Plasma monitoring: a challenge for and of the laboratory

Introduction: Therapeutic drug monitoring (TDM) of psychiatric patients is advisable, with the aim of reducing side effects and optimizing the therapy, and is a particularly useful tool if one considers the poor compliance of treated patients. Starting from clinical-chemical correlation data, TDM allows therapy personalization according to the specific needs of the patient. This in turn leads to increased patient compliance and to improved drug efficacy, and finally also to lower total treatment expenses, due to the reduction in hospitalisation length and frequency [1]. Methods: Performing the TDM obviously requires suitable analytical methods, consisting in two steps: sample pre-treatment and instrumental analysis. The first step is critical for the removal of biological interferences. The second step is usually carried out by liquid chromatography or capillary electrophoresis, coupled with different detectors, selected on the basis of the drug physico-chemical properties and expected plasma levels. Therefore, the methods and the corresponding techniques should possess adequate sensitivity and selectivity for the particular analytical problem. Results: Psychiatric patients are very often subjected to polypharmacy: for example, with antipsychotic and anxiolytic-hypnotic drugs for the treatment of schizophrenia; or with atypical antipsychotics (quetiapine, olanzapine) and antiepileptic agents (lamotrigine, oxcarbazepine) for bipolar disorder [2]. This fact constitutes a great challenge for both psychiatrists and analytical laboratories. Conclusions: The possibility of unwanted drug interactions is a constant threat during polypharmacy. Drug metabolism can be strongly influenced by the administration of other drugs, leading to possible toxicity, when a reduced metabolism is observed, or to a lack of response to therapy in the opposite case. The presence of numerous drugs and metabolites in the patient plasma makes the analytical problem, as well as the interpretation of the resulting plasma level data, much more complicated. At the same time, it is exactly this kind of challenge that makes it so exciting and interesting to work on plasma monitoring. References: [1] M.A. Raggi, R. Mandrioli, V. Pucci, C. Sabbioni, Advances in therapeutic drug monitoring of atypical antipsychotic drugs. Med. Chem. Rev. 1, 299–316 (2004). [2] A. Musenga, M.A. Saracino, G. Sani, M.A. Raggi, Antipsychotic and antiepileptic drugs in bipolar disorder: the importance of therapeutic drug monitoring. Curr. Med. Chem. 16, 1463–1481 (2009)