Stability of ten psychotropic drugs in formalin-fixed porcine liver homogenates.

ABSTRACT

In forensic toxicology studies, drug concentrations must be estimated by the analytical data of formalin-fixed tissues if fresh or frozen tissue specimens are not available. We wished to investigate the stability and time-course of metabolism/degradation of drugs in formalin-fixed tissues using porcine liver homogenates (PLHs) instead of human tissue. Ten psychotropic drugs (amitriptyline, brotizolam, diazepam, diphenhydramine, estazolam, etizolam, levomepromazine, paroxetine, quetiapine and triazolam) were added to PLHs. After the PLHs had been fixed with neutral buffered formalin at room temperature, the concentrations of the drugs in the PLHs were determined by liquid chromatography-tandem mass spectrometry after 3 days, 1 week, 2 weeks, 4 weeks, 2 months, 4 months and 6 months. After 6 months, the residual ratio of amitriptyline, diphenhydramine and quetiapine was 80 %-95 %; that of diazepam, paroxetine and triazolam was 10 %-45 %; and that of brotizolam, etizolam and levomepromazine was 1 %-5 %. Estazolam was not detected from the first day of formalin fixation. These data suggest that the concentrations of drugs in PLHs measured after formalin fixation decreased to varying degrees compared with their initial concentrations. These time-dependent changes in drug concentration were due to degradation during preservation in formalin solution and metabolism by hepatic microsomal enzymes.