Determination of succinyldicholine in different tissue samples from guinea pigs after injection of a single intravenous dose

Malthe‐Sørenssen, D.; Odden, Erling; Blanch, Jaime.; Bugge, Andreas; Mørland, J

doi:10.1016/0379-0738(86)90079-4

Cited by 6 publications

(6 citation statements)

References 8 publications

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“…Although far from being routine analysis, there exists a small number of previously published extraction methods for the parent drug, including protein precipitation1, 5 as well as solid‐phase extraction (SPE) schemes using C 1 ‐,6, 7 C 18 ‐12 and carboxylic acid (CBA)11‐cartridges. Liquid–liquid extraction (LLE) has equally been applied for sample clean‐up, the necessary ion‐pairing reagents being hexanitrodiphenylamine (DPA)13–15 or potassium triiodide (KI 3 ) 16. LeBeau et al 8 as well as Ballard et al 9 further reported a rather complex SUX extraction procedure, consisting of an LLE step in combination with reverse‐phase ion‐pairing SPE using heptafluorobutyric acid (HFBA) as the ion‐pairing reagent.…”

Section: Introductionmentioning

confidence: 99%

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A fully validated isotope dilution HPLC‐MS/MS method for the simultaneous determination of succinylcholine and succinylmonocholine in serum and urine samples

2008

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A high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method for the simultaneous detection of succinylcholine (SUX) and its metabolite succinylmonocholine (SMC) in serum and urine is presented. For internal standardization using isotope dilution, the deuterated compounds SUX-d(18) and SMC-d(3) were employed. Full validation was performed according to international guidelines. Solid-phase extraction (SPE) of acidified samples was accomplished using Strata-X polymeric reversed phase cartridges together with heptafluorobutyric acid (HFBA) as ion-pairing reagent. Separation was achieved within 13 min on a Phenomenex Synergi Hydro RP C18 column (4 microm, 150 x 2 mm) using a gradient of 5 mM ammonium formate buffer pH 3.5 and acetonitrile.To ensure the method's applicability in forensic as well as clinical toxicology, the specific demands of both research fields were taken into account, and the method was thus validated for a low and high concentration range. For both serum and urine as sample matrix, the validation revealed good intraday and interday precisions, consistently ranging below 15% for the lowest and below 10% for elevated concentrations. Accuracy was likewise good and never exceeded 10%. Extraction recovery was excellent, ranging between 88.1 and 103.9% for SUX and SMC in both tested matrices. Matrix effects were significant, the otherwise optimized extraction and detection methods, however, allowed for a very satisfactory sensitivity of the described method: For serum, the limits of detection and quantitation were determined to be 1.9 and 6.0 ng/ml for SUX, as well as 2.5 and 8.6 ng/ml for SMC, respectively; for urine, the corresponding values were established to be 1.4 and 4.0 ng/ml (SUX), as well as 1.5 and 4.9 ng/ml (SMC).The presented method was successfully applied to authentic samples of two forensic cases investigated in the institute of forensic medicine in Bonn, allowing the diagnosis of SUX intoxications.

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Section: Introductionmentioning

confidence: 99%

“…For the detection of SUX, several mass spectrometric approaches have been reported, including for example GC‐MS analysis of derivatized extracts13, 15 as well as DI/EI‐MS16 and HPLC‐ESI‐MS11 methods. Tandem‐MS techniques like DI/ESI‐MS/MS6, 7, 10 and HPLC‐MS/MS(MS)9, 12 have also been used previously.…”

Section: Introductionmentioning

confidence: 99%

A fully validated isotope dilution HPLC‐MS/MS method for the simultaneous determination of succinylcholine and succinylmonocholine in serum and urine samples

2008

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“…Various techniques have been employed for the detection of SUX ranging from thin‐layer chromatography12, 13 and gas chromatography of succinate esters12 to HPLC with electrochemical1, 3 or fluorescence detection,5 as well as to several approaches using mass spectrometric detection such as, for example, GC‐MS of derivatized extracts,14, 15 DI/EI‐MS16 and HPLC‐ESI‐MS 11. Lately, also tandem‐MS techniques like DI/ESI‐MS/MS6, 7, 10 and HPLC‐MS/MS(MS)9, 17 have been reported.…”

Section: Introductionmentioning

confidence: 99%

“…Only a minority of the latter authors employing a mass spectrometric detection method did use deuterated internal standards for quantification of SUX, i.e. SUX‐ d 6 ,6, 7 SUX‐ d 8 9 and SUX‐ d 12 14, 15…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and characterization of succinylcholine‐d₁₈ and succinylmonocholine‐d₃ designed for simultaneous use as internal standards in mass spectrometric analyses

2007

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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.

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Succinylcholin in der forensischen Toxikologie

2012

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Determination of succinyldicholine in different tissue samples from guinea pigs after injection of a single intravenous dose

Cited by 6 publications

References 8 publications

A fully validated isotope dilution HPLC‐MS/MS method for the simultaneous determination of succinylcholine and succinylmonocholine in serum and urine samples

A fully validated isotope dilution HPLC‐MS/MS method for the simultaneous determination of succinylcholine and succinylmonocholine in serum and urine samples

Synthesis and characterization of succinylcholine‐d₁₈ and succinylmonocholine‐d₃ designed for simultaneous use as internal standards in mass spectrometric analyses

Succinylcholin in der forensischen Toxikologie

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Determination of succinyldicholine in different tissue samples from guinea pigs after injection of a single intravenous dose

Cited by 6 publications

References 8 publications

A fully validated isotope dilution HPLC‐MS/MS method for the simultaneous determination of succinylcholine and succinylmonocholine in serum and urine samples

A fully validated isotope dilution HPLC‐MS/MS method for the simultaneous determination of succinylcholine and succinylmonocholine in serum and urine samples

Synthesis and characterization of succinylcholine‐d18 and succinylmonocholine‐d3 designed for simultaneous use as internal standards in mass spectrometric analyses

Succinylcholin in der forensischen Toxikologie

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Synthesis and characterization of succinylcholine‐d₁₈ and succinylmonocholine‐d₃ designed for simultaneous use as internal standards in mass spectrometric analyses