Simultaneous serum determination of butyrophenones in automated column-switching high-performance liquid chromatography

Abstract

Introduction: Butyrophenones are widely used for the treatment of psychoses and are frequently encountered in clinical toxicology, clinical pharmacology and forensic chemistry. This chemical class of antipsychotics tend to have a narrow therapeutic range and the quantity required to be effective is near to the quantity that causes significant side effects. Maintaining their steady state poses therefore a problem for the therapy. The rates at which individuals absorb, metabolize and eliminate drugs are based upon their age, general state of health, genetic makeup, and the interference of other medications. Therefore, the therapeutic drug monitoring of the selected butyrophenone serum concentrations plays an important role in the selection of the optimum dose for the therapy. This research method is aimed at the simultaneous quantification of benperidol, bromperidol and haloperidol without any pre-treatment step, which will help for a faster routine control. It is also aimed to be as specific as possible in separating other butyrophenones and similar substances in human serum for a better control of their different therapeutic concentrations. Materials and Methods: The chromatographic separation of the antipsychotics used in the experiment so far was performed with a C18 reversed-phased column with acetonitril and water (milli-Q) as eluent and with the help of an UV detector. The pool serum was obtained from the university clinic Regensburg. All chemicals used were of the highest purity commercially available. The raw materials used so far for the experiment was obtained from different pharmaceutical companies in Germany. The standard stock solutions of these raw substances were prepared by dissolving a properly weighed amount of the named substances in methanol to produce a standard solution. The diluted solutions were spiked in serum to yield the final concentrations for the measurement. The prepared butyrophenone serum concentrations were then injected in the HPLC-System for their chromatographic measurements. Result: The obtained results were very encouraging, the compounds were well separated reproducing a very good percentage amount in comparison with the expected added amount. So far, the three compounds showed good linearity with a detection limit of 2 ng/ml. Imprecision and inaccuracy that may occur during the experimental work has not yet been fully validated, because the research work is still successfully going on and very promising. The aim of getting a lower limit of detection is being targeted at and it is progressing. Conclusion: The advantage of this research work lies not only on its effectivity, but it is also a quicker method in the determination of serum antipsychotic concentrations. It is very practicable in case of any emergency and it also opens the possibility for quicker results of TDM routine measurements. It will also minimize the expenditure for the routine determination of a large set of individual and varying drug combinations.