Determination of new pyrrolidino cathinone derivatives, PVT, F-PVP, MPHP, PV8, PV9 and F-PV9, in human blood by MALDI-Q-TOF mass spectrometry

A rapid and sensitive detection method using matrix-assisted laser desorption ionization (MALDI)-quadrupole time-of-flight-mass spectrometry (Q-TOF-MS) was developed for the analysis of six pyrrolidino cathinone derivatives, alpha-pyrrolidinopentiothiophenone (PVT), 4'-fluoro-alpha-pyrrolidinopentiophenone (F-PVP), 4'-methyl-alpha-pyrrolidinohexanophenone (MPHP), alpha-pyrrolidinoheptanophenone (PV8), alpha-pyrrolidinooctanophenone (PV9) and 4'-fluoro-alpha-pyrrolidinooctanophenone (F-PV9), that were newly designated as illegal drugs in Japan. In this method, alpha-cyano-4-hydroxycinnamic acid was used as the matrix to assist the ionization of cathinones. MS spectra of these cathinones showed a protonated molecule [M+H](+) and iminium, respectively, and hence the main ions of MALDI-MS were a mixture of the main ions detected by liquid chromatography-electrospray ionization-mass spectrometry and that by gas chromatography-electron ionization-mass spectrometry. The quantification of these cathinones was performed using alpha-pyrrolidinopentiophenone as the internal standard. The limit of detection was 1 ng/ml and the quantification range was 2-100 ng/ml for these cathinones using 20 mu l of blood. We encountered a fatal poisoning case where PV9 was abused. The PV9 levels in postmortem blood samples from the right heart, left heart and femoral vein were 198, 209 and 163 ng/ml, respectively. The metabolites of PV9 were detected, and the peak height of an oxidized metabolite was higher than those of the protonated molecule and the other metabolites.