Distribution measurement of amphetamine-type stimulants in organs using micropulverized extraction and liquid chromatography/tandem mass spectrometry to complement drug distribution using mass spectrometry imaging.

Amphetamine-type stimulants (ATS) such as methamphetamine are widely abused and can cause toxic effects in the body. In this study, a simple and accurate analytical method for distribution measurement of drugs in organs was developed to visualize localization of ATS in organs and to complement drug distribution by mass spectrometry imaging (MSI). The brain, liver and kidney from rats to which ATS had been administered were segmented into blocks of 2×2×2 mm3 at -30°C. Each organ block was micropulverized with a stainless-steel bullet at -80°C. The concentrations of drugs in each block were measured by liquid chromatography/tandem mass spectrometry. The three-dimensional distribution of drugs in a whole organ was expressed using color gradation of drug concentration after reconstruction of all blocks to the original locations. The distribution was also compared with that obtained by MSI. This method enabled measurement of drug distribution in organs with simple and clean procedures and accurate quantification unlike autoradiography and MSI. The methamphetamine concentrations were different between parts in an organ, particularly in the kidney. This method could be applicable to the measurement of the distribution of compounds in various solid samples and could be used as a complementary method for the measurement of the distribution of compounds by MSI.