Skip to main content
SpringerLink
Log in

Degradation and elimination of succinylcholine and succinylmonocholine and definition of their respective detection windows in blood and urine for forensic purposes

  • Original Article
  • Published:
International Journal of Legal Medicine Aims and scope Submit manuscript

Abstract

The muscle relaxant succinylcholine (SUX) evokes respiratory paralysis, and numerous cases of fatal SUX intoxication have been reported. Detection of SUX and its metabolite succinylmonocholine (SMC) is difficult, both due to their (bis-) quaternary structure and the extreme hydrolytic susceptibility of SUX, and data on degradation kinetics of SUX and SMC is scarce. The present study investigates the in vivo and in vitro degradation as well as elimination of both target analytes using authentic blood and urine samples from anesthetized patients. With a special focus on the urinary data and stabilization issues, this work intends to considerably enhance the forensic knowledge concerning SUX intoxications and to present the reader with practical analytical strategies to cope with such difficult cases. Eighteen subjects undergoing surgery and requiring arterial as well as bladder catheters were included in this study. Muscle relaxation was initialized with a bolus injection of 80–100 mg SUX. Blood and urine samples were either collected using paraoxonized (n = 15) or non-modified (n = 3) tubes. Sampling was performed within 6 h after SUX application following a pre-assigned schedule. Samples were processed according to a validated isotope dilution HPLC–MS/MS method using ion-pair solid-phase extraction. In blood, SUX was usually detectable for up to 10 min post-injection, while detection of SMC was possible over the whole observation period of 6 h. Effectiveness of organophosphate stabilization was proven for both analytes and is therefore recommended. In freshly secreted urine, detection windows of a minimum of 2 h as opposed to 6 h have been determined for SUX versus SMC, respectively. Considering SMC plasma kinetics, detection of the metabolite in blood and freshly secreted urine appears to be possible over a period of at least 8–24 h. Paraoxon did not enhance the stability of either target substance in urine, stabilization of urine samples is nonetheless recommended. In summary, SMC was proven to be the most promising target analyte in SUX analysis, with urine being the proposed matrix of choice for forensic applications. Furthermore, our work defines meaningful detection windows for SUX and SMC in blood and urine as routine matrices and presents sampling recommendations as well as guideline values for forensic toxicological analysis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Abbreviations

SUX:

Succinylcholine

SMC:

Succinylmonocholine

HPLC-(ESI-)MS/MS:

High performance liquid chromatography-(electrospray ionization-)tandem mass spectrometry

LOD:

Limit of detection

SPE:

Solid-phase extraction

References

  1. Maltby JR (1975) Criminal poisoning with anaesthetic drugs: murder, manslaughter, or not guilty. Forensic Sci 6:91–108

    Article  PubMed  CAS  Google Scholar 

  2. Strock D, Kuczkowski KM, Greenberg M (2004) Accidental administration of succinylcholine for the treatment of hypotension in a labouring parturient. Can J Anaesth 51:853–854

    Article  PubMed  Google Scholar 

  3. Somogyi G, Varga M, Prokai L, Dinya Z, Buris L (1989) Drug identification problems in two suicides with neuromuscular blocking agents. Forensic Sci Int 43:257–266

    Article  PubMed  CAS  Google Scholar 

  4. Kato M, Shiratori T, Yamamuro M, Haga S, Hoshi K, Matsukawa S, Jalal IM, Hashimoto Y (1999) Comparison between in vivo and in vitro pharmacokinetics of succinylcholine in humans. J Anesth 13:189–192

    Article  PubMed  CAS  Google Scholar 

  5. Dal Santo G (1968) Kinetics of distribution of radioactive labeled muscle relaxants. Anesthesiology 29:435–443

    Article  PubMed  CAS  Google Scholar 

  6. Pitts NI, Deftereos D, Mitchell G (2000) Determination of succinylcholine in plasma by high-pressure liquid chromatography with electrochemical detection. Br J Anaesth 85:592–598

    Article  PubMed  CAS  Google Scholar 

  7. Torda TA, Graham GG, Warwick NR, Donohue P (1997) Pharmacokinetics and pharmacodynamics of suxamethonium. Anaesth Intensive Care 25:272–278

    PubMed  CAS  Google Scholar 

  8. Lagerwerf AJ, Vanlinthout LE, Vree TB (1991) Rapid determination of succinylcholine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr 570:390–395

    Article  PubMed  CAS  Google Scholar 

  9. Roy JJ, Boismenu D, Gao H, Mamer OA, Varin F (2001) Measurement of succinylcholine concentration in human plasma by electrospray tandem mass spectrometry. Anal Biochem 290:238–244

    Article  PubMed  CAS  Google Scholar 

  10. Roy JJ, Donati F, Boismenu D, Varin F (2002) Concentration–effect relation of succinylcholine chloride during propofol anesthesia. Anesthesiology 97:1082–1092

    Article  PubMed  CAS  Google Scholar 

  11. Lehmann H, Silk E (1953) Succinylmonocholine. Br Med J 1:767–768

    Article  PubMed  CAS  Google Scholar 

  12. Foldes FF, Vandervort RS, Shanor SP (1955) The fate of succinylcholine in man. Anesthesiology 16:11–21

    Article  PubMed  CAS  Google Scholar 

  13. Foldes FF (1953) Succinylmonocholine iodide: its enzymatic hydrolysis and neuromuscular activity. Proc Soc Exp Biol Med 83:187–189

    PubMed  CAS  Google Scholar 

  14. Ballard KD, Vickery WE, Nguyen LT, Diamond FX, Rieders F (2006) 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. J Am Soc Mass Spectrom 17:1456–1468

    Article  PubMed  CAS  Google Scholar 

  15. LeBeau M, Quenzer C (2003) Succinylmonocholine identified in negative control tissues. J Anal Toxicol 27:600–601

    PubMed  CAS  Google Scholar 

  16. Kuepper U, Musshoff F, Madea B (2008) A fully validated isotope dilution HPLC-MS/MS method for the simultaneous determination of succinylcholine and succinylmonocholine in serum and urine samples. J Mass Spectrom 43:1344–1352

    Article  PubMed  CAS  Google Scholar 

  17. Kuepper U, Musshoff F, Madea B (2007) Synthesis and characterization of succinylcholine-d(18) and succinylmonocholine-d(3) designed for simultaneous use as internal standards in mass spectrometric analyses. J Mass Spectrom 42:929–939

    Article  PubMed  CAS  Google Scholar 

  18. Kuepper U, Musshoff F, Madea B (2008) Succinylmonocholine analytics as an example for selectivity problems in high-performance liquid chromatography/tandem mass spectrometry, and resulting implications for analytical toxicology. Rapid Commun Mass Spectrom 22:1965–1970

    Article  PubMed  CAS  Google Scholar 

  19. Kuepper U, Musshoff F, Hilger RA, Herbstreit F, Madea B (2011) Pharmacokinetic properties of succinylmonocholine in surgical patients. J Anal Toxicol 35:302–311

    Article  PubMed  CAS  Google Scholar 

  20. Hoshi K, Hashimoto Y, Matsukawa S (1993) Pharmacokinetics of succinylcholine in man. Tohoku J Exp Med 170:245–250

    Article  PubMed  CAS  Google Scholar 

  21. Forney RB Jr, Carroll FT, Nordgren IK, Pettersson BM, Holmstedt B (1982) Extraction, identification and quantitation of succinylcholine in embalmed tissue. J Anal Toxicol 6:115–119

    PubMed  CAS  Google Scholar 

  22. Nordgren I, Baldwin K, Forney R Jr (1984) Succinylcholine-tissue distribution and elimination from plasma in the dog. Biochem Pharmacol 33:2519–2521

    Article  PubMed  CAS  Google Scholar 

  23. Foldes FF, Norton S (1954) The urinary excretion of succinyldicholine and succinylmonocholine in man. Br J Pharmacol Chemother 9:385–388

    PubMed  CAS  Google Scholar 

  24. Stevens HM, Moffat AC (1974) A rapid screening procedure for quaternary ammonium compounds in fluids and tissues with special reference to suxamethonium (succinylcholine). J Forensic Sci Soc 14:141–148

    Article  PubMed  CAS  Google Scholar 

  25. Goedde HW, Held KR, Altland K (1968) Hydrolysis of succinyldicholine and succinylmonocholine in human serum. Mol Pharmacol 4:274–287

    PubMed  CAS  Google Scholar 

  26. Schmidinger S, Held KR, Goedde HW (1966) Hydrolysis of succinyldicholine by pseudocholinesterase at low concentrations. Humangenetik 2:221–224

    Article  PubMed  CAS  Google Scholar 

  27. Tsutsumi H, Nishikawa M, Katagi M, Tsuchihashi H (2003) Adsorption and stability of suxamethonium and its major hydrolysis product succinylmonocholine using liquid chromatography-electrospray ionization mass spectrometry. J Health Sci 49:285–291

    Article  CAS  Google Scholar 

  28. Mtairag EM, Abdelghaffar H, Labro MT (1994) Investigation of dirithromycin and erythromycylamine uptake by human neutrophils in vitro. J Antimicrob Chemother 33:523–536

    Article  PubMed  CAS  Google Scholar 

  29. Uetrecht JP (1992) Metabolism of clozapine by neutrophils. Possible implications for clozapine-induced agranulocytosis. Drug Saf 7(Suppl 1):51–56

    Article  PubMed  CAS  Google Scholar 

  30. Baldwin KA, Forney R Jr (1988) The influence of storage temperature and chemical preservation on the stability of succinylcholine in canine tissue. J Forensic Sci 33:462–469

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Forensic Medicine, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany

    Uta Kuepper

  2. Klinik für Anästhesiologie & Intensivmedizin, Universität Duisburg-Essen and Universitätsklinikum Essen, Hufelandstrasse 55, 45147, Essen, Germany

    Frank Herbstreit & Jürgen Peters

  3. Institute of Forensic Medicine, University of Bonn, Stiftsplatz 12, 53111, Bonn, Germany

    Uta Kuepper, Burkhard Madea & Frank Musshoff

Authors
  1. Uta Kuepper
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frank Herbstreit
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jürgen Peters
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Burkhard Madea
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Frank Musshoff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Uta Kuepper.

Additional information

Uta Kuepper and Frank Herbstreit share equal authorship.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kuepper, U., Herbstreit, F., Peters, J. et al. Degradation and elimination of succinylcholine and succinylmonocholine and definition of their respective detection windows in blood and urine for forensic purposes. Int J Legal Med 126, 259–269 (2012). https://doi.org/10.1007/s00414-011-0623-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00414-011-0623-0

Keywords

Search

Navigation