title: Pharmacokinetic properties of succinylmonocholine in surgical patients.
abstract: Intoxications with succinylcholine (SUX) lead to a potentially lethal respiratory paralysis, and forensic cases involving accidental or deliberate SUX-application have been reported. Detection of SUX as well as its metabolite succinylmonocholine (SMC) is difficult: both substances are analytically challenging, and the extremely short plasma half-life of SUX additionally hampers detection of the parent compound. Pharmacokinetic data are scarce on SUX and non-existent on SMC. To enhance forensic knowledge concerning SUX intoxications, plasma pharmacokinetics of SMC were investigated in anesthetized patients. Fifteen subjects scheduled for a surgical procedure were included in this study. Muscle-relaxation was initialized with a bolus injection of 80-100 mg SUX. Blood sampling was performed within 6 h after SUX application using paraoxonized tubes. Collected plasma was processed according to a validated isotope dilution high-performance liquid chromatography-tandem mass spectrometry method using ion-pair solid-phase extraction. Pharmacokinetic parameters were derived from a user-defined as well as a three-compartment model. For SMC, peak plasma concentrations were reached after 0.03-2.0 min. In contrast to SUX, SMC was more slowly and more extensively distributed, featuring triphasic plasma concentration time profiles. Pharmacokinetic key parameters were subject to interindividual variation of potential forensic importance, with terminal half-lives of 1-3 h indicating a detection interval of 8-24 h for SMC in plasma. SMC was proven to be the only realistic SUX marker in a forensic context. The present work defines meaningful detection windows for plasmatic SMC after SUX application and offers guideline values for forensic toxicological casework.
authors.affiliation: Institute of Forensic Medicine, University Hospital Essen, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Kuepper
authors.forename: Frank
authors.initials: F
authors.lastname: Musshoff
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Hilger
authors.forename: Frank
authors.initials: F
authors.lastname: Herbstreit
authors.forename: Burkhard
authors.initials: B
authors.lastname: Madea
mesh_terms: D000328:Adult; D000368:Aged; D001774:Blood Chemical Analysis; D005260:Female; D053593:Forensic Toxicology; D006207:Half-Life; D006801:Humans; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D009467:Neuromuscular Depolarizing Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D011041:Poisoning / Q000097:blood / Q000175:diagnosis; D013390:Succinylcholine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D009467:Neuromuscular Depolarizing Agents; C035798:succinylmonocholine; D013390:Succinylcholine