title: Bacterial degradation of risperidone and paliperidone in decomposing blood.
abstract: The stability of two benzisoxazole antipsychotics was determined in vitro in decomposing porcine blood inoculated with bacteria, utilizing a high-performance liquid chromatography with ultraviolet and fluorescence detection method for drug quantitation. Stability experiments for risperidone and paliperidone were conducted at 7, 20 and 37°C for 4 days using sterile and bacterially inoculated porcine blood. The drugs were stable in sterile blood at each temperature and in inoculated blood at 7°C, but degraded significantly in inoculated blood at 20 and 37°C. Complete loss occurred within 2 days when incubated at 37°C. The benzisoxazole-cleaved degradation products for both drugs were identified as 2-hydroxybenzoyl-risperidone and 2-hydroxybenzoyl-paliperidone utilizing liquid chromatography quadrupole-time-of-flight mass spectrometry and accurate mass measurements. The degradation products have been found in postmortem case studies, including one case where risperidone and paliperidone were not detected, indicating complete conversion can occur in situ.
authors.affiliation: School of Chemical and Physical Sciences, Flinders University, Bedford Park, SA, 5042, Australia. danielle.butzbach@sa.gov.au
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Butzbach
authors.forename: Peter C
authors.initials: PC
authors.lastname: Stockham
authors.forename: Hilton J
authors.initials: HJ
authors.lastname: Kobus
authors.forename: D Noel
authors.initials: DN
authors.lastname: Sims
authors.forename: Roger W
authors.initials: RW
authors.lastname: Byard
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lokan
authors.forename: George Stewart
authors.initials: GS
authors.lastname: Walker
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D053593:Forensic Toxicology; D006094:Gram-Positive Bacteria / Q000378:metabolism*; D007555:Isoxazoles / Q000097:blood*; D000068882:Paliperidone Palmitate; D011180:Postmortem Changes; D011743:Pyrimidines / Q000097:blood*; D018967:Risperidone / Q000031:analogs & derivatives / Q000097:blood*; D013048:Specimen Handling; D021241:Spectrometry, Mass, Electrospray Ionization; D013552:Swine; D013696:Temperature
chemical_list: C583077:2-hydroxybenzoylpaliperidone; C583076:2-hydroxybenzoylrisperidone; D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D018967:Risperidone; D000068882:Paliperidone Palmitate