Clinical Case Study
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article. Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest: Employment or Leadership: None declared. Consultant or Advisory Role: None declared. Stock Ownership: None declared. Honoraria: None declared. Research Funding: None declared. Expert Testimony: None declared. Patents: None declared. Other Remuneration: R.A. Middleberg, AACC symposium.
References 1. Ross EA, Watson M, Goldberger B. “Bath salts” intoxication. N Engl J Med 2011;365:967– 8. 2. American Association of Poison Control Centers. Poison control centers applaud DEA’s ban of bath salts. http://www.aapcc.org/dnn/Portals/0/
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DEA%20Ban%20on%20Bath%20Salts%209.8.2011.pdf (Accessed November 2011). Caravati EM, McCowan CL, Marshall SW. Plants. In: Dart RC, ed. Medical toxicology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2004. p 1707– 8. Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol 2012;8:33– 42. Spiller HA, Ryan ML, Weston RG, Jansen J. Clinical experience with and analytical confirmation of “bath salts” and “legal highs” (synthetic cathinones) in the United States. Clin Toxicol (Phila) 2011;49:499 –505. Coppola M, Mondola R. 3,4-methylenedioxypyrovalerone (MDPV): chemistry, pharmacology and toxicology of a new designer drug of abuse marketed online. Toxicol Lett 2012;208:12–5. Newton TF, Kalechstein AD, Hardy DJ, Cook IA, Nestor L, Ling W, Leuchter AF. Association between quantitative EEG and neurocognition in methamphetamine-dependent volunteers. Clin Neurophysiol 2004;115: 194 – 8. Paulus MP, Hozack NE, Zauscher BE, Frank L, Brown GG, Braff DL, Schuckit MA. Behavioral and functional neuroimaging evidence for prefrontal dysfunction in methamphetamine-dependent subjects. Neuropsychopharmacology 2002;26:53– 63. Department of Justice, Drug Enforcement Administration. Schedules of controlled substances: temporary placement of three synthetic cathinones into Schedule I. Codified at 21 CFR Part 1308. Fed Regist 2011;76:65371–5. Westphal F, Junge T, Rosner P, Sonnichsen F, Schuster F. Mass and NMR spectroscopic characterization of 3,4-methylenedioxypyrovalerone: a designer drug with ␣-pyrrolidinophenone structure. Forensic Sci Int 2009;190: 1– 8.
Commentary Michael E. Mullins*
In late 2010, “bath salts” appeared on the scene in North America and exploded with 6138 humanexposure calls to US poison control centers in 2011 (1, 2 ). Although only 1717 cases have been reported to poison centers as of June 30, 2012, the number of cases has increased for 6 consecutive months (3 ). Because the American Association of Poison Control Centers database depends on voluntary reporting, the current numbers certainly underestimate the magnitude of the epidemic as emergency physicians become more familiar with bath salt exposures. The regulatory response by state and federal authorities was much swifter than in previous drug trends. Until we have complete data for 2012, we may not know the full effect of the legal restrictions on bath salts. From data provided by the US Drug Enforcement Administration, the most frequently seized “bath salts” are mephedrone (4-methyl-N-methylcathinone) and
Division of Emergency Medicine, Washington University School of Medicine, St. Louis, MO. * Address correspondence to the author at: Washington University School of Medicine, Campus Box 8072, 660 S. Euclid Ave., St. Louis, MO 63110. E-mail
[email protected]. Received July 15, 2012; accepted August 3, 2012. DOI: 10.1373/clinchem.2012.191114
MDPV (3,4-methylenedioxypyrovalerone). Others include methcathinone (N-methylcathinone), methylone (methylenedioxy-N-methylcathinone), and 4-MEC (4-methyl-N-ethylcathinone) (2 ). Cathinone derivatives (bath salts) and amphetamine derivatives have strikingly similar 2-dimensional structures, often differing principally in the ketone at the  carbon. Yet, the cathinones tend not to produce positive results in urine screens for amphetamine. Because advanced laboratory techniques are usually not routinely and rapidly available in most hospitals, the emergency physician may be left in a diagnostic quandary when a patient with apparent sympathomimetic toxidrome (agitation with tachycardia, hyperthermia, and/or hyperthermia) fails to display cocaine metabolites or amphetamines in the urine drug screen. Fortunately, the treatment is similar and usually includes benzodiazepines or antipsychotic tranquilizers, repletion of fluids and electrolytes (especially potassium), and sometimes control of temperature or blood pressure (3 ). Randox Toxicology has recently marketed an immunoassay for cathinone derivatives (5 ), and Ameritox has developed a mass spectrometry test (6 ). These tests may be useful for emergency physicians and for law enforcement, especially in areas with a high prevalence of bath salt use. Clinical Chemistry 59:4 (2013) 615
Clinical Case Study
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article. Authors’ Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
References 1. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Dart RC. 2010 Annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 28th annual report. Clin Toxicol (Phila) 2011;49: 910 – 41.
2. U.S. Department of Justice, Drug Enforcement Administration, Office of Diversion Control. Special report: synthetic cannabinoids and synthetic cathinones reported in NFLIS, 2009 –2010. https://www.nflis.deadiversion.usdoj.gov/ DesktopModules/ReportDownloads/Reports/SynCannabSynCath.pdf (Accessed July 2012). 3. American Association of Poison Control Centers. Poison Help: bath salts data, updated July 6, 2012. http://www.aapcc.org/dnn/Portals/0/Bath%20Salts%20 Data%20for%20Website%207.06.2012.pdf (Accessed July 2012). 4. Spiller HA, Ryan ML, Weston RG, Jansen J. Clinical experience with and analytical confirmation of “bath salts” and “legal highs” (synthetic cathinones) in the United States. Clin Toxicol 2011;49:499 –505. 5. Randox Toxicology. Mephedrone/methcathione ELISA. http://www. randoxtoxicology.com/Products/Mephedrone-Methcathinone-ELISA-p-313 (Accessed July 2012). 6. Ameritox. Bath salts: With dangerous drug use on the rise, Ameritox launches critical new test to help detect designer drug. http://www.ameritox.com/bathsalts-with-dangerous-drug-use-on-the-rise-ameritox-launches-critical-newtest-to-help-detect-designer-drug/ (Accessed July 2012).
Commentary Gwendolyn A. McMillin*
Designer drugs such as “bath salts” are not detected by routine toxicology tests. As demonstrated by this case report, a patient suspected of intoxication with a designer drug is managed with supportive care, suggesting that identification of the specific toxicant may not contribute to making management decisions for the patient experiencing acute poisoning. Detection of a particular toxicant, however, may affect long-term management decisions and may have forensic and/or social implications. Collection of both blood and urine samples is recommended to maximize the likelihood of drug detection. An analytical method that does not detect drug metabolites may not be appropriate for urine, a specimen in which metabolites are likely to predominate. The patterns of metabolites that appear in the urine after the use of “bath salts” are not well known. In the presented clinical case, a blood sample was sufficient to successfully identify the synthetic cathinone involved. It is important to note that the cathinones are unstable in whole blood and sample extracts under neutral conditions, a consideration that makes sample handling critical for detection (1 ). The authors indicate that mass spectrometry is the best technology for detecting designer drugs. Although mass spectrometry is a valuable tool and several pub-
lished methods using this technology are available, targeted methods designed to detect specific masses are not analytically sensitive for all designer drugs. In addition, the chemistry of the specific drug(s) will dictate the most appropriate methods of sample preparation and extraction. Underground chemists frequently make chemical modifications to drugs, making detection a continuous challenge for laboratories. A method designed to detect a wide range of masses (full-scan mode) coupled with several approaches to sample preparation may be required to detect use of a designer drug (2 ). In summary, the optimal approach for the detection of designer drug use is not well defined and requires coordination of sample collection and handling, as well as application of specialized analytical methods.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article. Authors’ Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
References Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT. * Address correspondence to the author at: ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108. Fax 801-584-5207; e-mail gwen.mcmillin@ aruplab.com. Received June 17, 2012; accepted June 28, 2012. DOI: 10.1373/clinchem.2012.191122
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1. Sorensen LK. Determination of cathinones and related ephedrines in forensic whole-blood samples by liquid-chromatography-electrospray tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2011;879: 727–36. 2. Dickson AJ, Vorce SP, Levine B, Past MR. Multiple-drug toxicity caused by the coadministration of 4-methylmethcathinone (mephedrone) and heroin. J Anal Toxicol 2010;34:162– 8.
