Bipolar disorder: Development of an UHPLC-UV method for the determination of 8 psychiatric drugs in human serum

Introduction: With a prevalence of approximately 3%, bipolar disorder is a quite common psychiatric disease. Therapeutic drug monitoring (TDM) can be a helpful tool to optimize the therapy: The concentration of a drug in human blood (measured via HPLC-UV), not simply the dosage, is responsible for its efficacy. With this background a new UHPLC-UV method was developed for TDM-guided treatment of bipolar patients. UHPLC runs at higher pressure with smaller columns than HPLC and allows faster and more sensitive analysis of small samples (10 µl injection volume). Method: The separation was performed on a RP-C18 column with a run time of 20 minutes. The mobile phase consists of phosphate buffer pH 3/MeOH 90:10 and ACN with gradient elution from 10 to 30% ACN with a flow rate of 0.5 ml/min. The drugs are monitored using UV-detection (209 and 230 nm). Results: This method allows a rapid analysis of 8 psychiatric drugs in human serum. Comparing the analysis of Aripiprazole (ARI) and its metabolite Dehydroaripiprazole (DARI) with UHPLC and HPLC shows the advantages of the UHPLC method: The UHPLC-analysis has a run time of only 20 minutes (HPLC: 40 min) with retention times of 14,1 min (ARI) and 13,1 min (DARI) (HPLC: 30,5 min (ARI) and 27,7 min (DAR)). The new developed method is faster and needs less solvent. This allows rapid and cost saving analysis of psychiatric drugs in daily routine. Prospect: The new method has to be validated to be used in daily routine at the TDM laboratory.