An analytical strategy for quaternary ammonium neuromuscular blocking agents in a forensic setting using LC-MS/MS on a tandem quadrupole/time-of-flight instrument.
An analytical strategy is described for analyzing quaternary ammonium neuromuscular blocking agents in a wide variety of biological specimens in a forensic setting. Neuromuscular blocking agents such as succinylcholine, pancuronium, and tubocurarine, often used as paralytic agents during surgery, are occasionally suspected as paralytic poisoning agents involved in suspected homicide and suicide cases. Because suspicion in such cases can develop slowly, the age, nature, and quality of available specimens varies greatly. The compounds are challenging analytically because of their simultaneous precharged yet lipophilic character. An analytical strategy has been devised for extracting these compounds from complex matrices using a combination of a modified Bligh and Dyer liquid-liquid extraction (used in reverse) followed by reverse-phase ion pairing solid-phase extraction using heptafluorobutyric acid as an ion pairing reagent. Final analysis is by LC-MS/MS using a tandem quadrupole orthogonal acceleration time of flight instrument (Q-TOF) with repetitive product ion scanning at high resolution. Native and spiked specimens are compared for both quantitative and especially qualitative purposes. The method has been applied to a wide variety of fluid and tissue specimen types, including numerous specimens from exhumation autopsies. For most specimens, detection limits are in the 2 to 10 ng/g range. Succinylmonocholine has been demonstrated to be present at low levels in normal posthumous kidney and liver. The Q-TOF is an excellent platform for forensic analytical investigations. This analytical strategy should also be applicable to other problematic analytes and sample matrices.
Ballard
Kevin D
KD
Research and Development, NMS Labs, 3701 Welsh Rd., 19090, Willow Grove, PA, USA. kevin.ballard@nmslab.com.
Vickery
William E
WE
Research and Development, NMS Labs, 3701 Welsh Rd., 19090, Willow Grove, PA, USA.
Nguyen
Loan T
LT
Research and Development, NMS Labs, 3701 Welsh Rd., 19090, Willow Grove, PA, USA.
Diamond
Francis X
FX
Research and Development, NMS Labs, 3701 Welsh Rd., 19090, Willow Grove, PA, USA.
Rieders
Fredric
F
The Fredric Rieders Family Renaissance Foundation, Willow Grove, Pennsylvania, USA.
D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D004950:Esterases / Q000037:antagonists & inhibitors; D053593:Forensic Toxicology; D006801:Humans; D007202:Indicators and Reagents; D008099:Liver / Q000737:chemistry; D009465:Neuromuscular Agents / Q000032:analysis* / Q000097:blood; D000644:Quaternary Ammonium Compounds / Q000032:analysis* / Q000097:blood; D012015:Reference Standards; D053719:Tandem Mass Spectrometry
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D009465:Neuromuscular Agents; D000644:Quaternary Ammonium Compounds; D004950:Esterases