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Synthesis and characterization of succinylcholine‐ d 18 and succinylmonocholine‐ d 3 designed for simultaneous use as internal standards in mass spectrometric analyses
Author(s) -
Kuepper Uta,
Musshoff Frank,
Madea Burkhard
Publication year - 2007
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.1230
Subject(s) - chemistry , yield (engineering) , mass spectrometry , chromatography , high performance liquid chromatography , succinic anhydride , tandem mass spectrometry , succinic acid , nuclear magnetic resonance spectroscopy , deuterium , organic chemistry , materials science , metallurgy , physics , quantum mechanics
Succinylcholine (SUX) is a routinely used yet potentially lethal depolarizing muscle relaxant, the detection of which poses severe problems to the clinical or forensic analyst: within a few minutes after its in vivo administration, SUX is broken down via succinylmonocholine (SMC) to yield the endogenous substances succinic acid and choline. For quantification of SUX and SMC in biological matrices using mass spectrometric detection, appropriate internal standards, i.e. deuterated analogs of the above substances, are indispensable but not commercially available. Internal standards for both substances were hence tailored to fit the analytical needs. The two‐step synthesis and subsequent characterization of SUX‐ d 18 and SMC‐ d 3 using a combination of nuclear magnetic resonance (NMR) spectroscopy, fast atom bombardment mass spectroscopy (FAB‐MS) and high‐performance liquid chromatography/tandem mass spectrometry (HPLC‐MS/MS) are described. SUX‐ d 18 was synthesized by reacting ethanolamine and iodomethane‐ d 3 in a first quaternization step to choline‐ d 9 , which in turn was esterified with succinyldichloride to yield the final product. SMC‐ d 3 was produced by esterification of succinic acid anhydride with dimethylaminoethanol, yielding desmethyl‐SMC as intermediate product. The latter was then reacted with iodomethane‐ d 3 to obtain SMC‐ d 3 . 1 H‐ and 13 C‐NMR data support the identity and purity as well as the designated deuteration of both preparations, findings which were further confirmed by FAB‐MS as well as HPLC‐MS/MS. Owing to a thoughtful design, the obtained substances SUX‐ d 18 and SMC‐ d 3 feature different deuteration patterns at their trimethylamine moieties, and thus finally offer the possibility to simultaneously quantify SUX and SMC in clinical as well as forensic samples using isotope dilution mass spectrometry. Copyright © 2007 John Wiley & Sons, Ltd.