Antemortem and Postmortem Methamphetamine Blood ...

1 Journal of Analytical toxicology 2013;37:386 389. Advance Access publication May 29, 2013 Case Report Antemortem and Postmortem Methamphetamine Blood Concentrations: Three Case Reports Iain M. McIntyre1*, Craig L. Nelson2, Bethann Schaber2 and Catherine E. Hamm1. 1. Forensic toxicology Laboratory, County of San Diego Medical Examiner's Of ce, 5570 Overland Ave., Suite 101, San Diego, CA 92123, USA, and 2 Department of Forensic Pathology, County of San Diego Medical Examiner's Of ce, 5570 Overland Ave., Suite 101, San Diego, CA 92123, USA. *Author to whom correspondence should be addressed. Email: We compare Antemortem whole - Blood to Postmortem peripheral Blood Blood -to-peripheral Blood (C/P) ratios were found to average concentrations of Methamphetamine and its metabolite amphetamine (+ ), and liver to peripheral Blood (L/P) ratios averaged in three medical examiner cases.

2 Antemortem specimens, initially (+ ). Comparable data were found for amphetamine. Downloaded from by guest on 24 May 2019. screened positive for Methamphetamine by ELISA, were subsequently These data showed a smaller average C/P ratio than that previ- confirmed, together with the Postmortem specimens, by GC-MS ana- ously reported by Barnhart et al. (11), but established that meth- lysis following solid-phase extraction. Methamphetamine peripheral amphetamine and amphetamine were most likely prone to some Blood to Antemortem Blood ratios averaged (+ + ; n 5 3) and degree of Postmortem redistribution (PMR). However, since amphetamine peripheral Blood to Antemortem Blood ratios averaged there was no opportunity for analyses in both Antemortem and (n 5 2). These data show that Postmortem redistribution occurs Postmortem specimens from the same individuals, a direct as- for both Methamphetamine and amphetamine, revealing that post- sessment of the degree of PMR could not be determined.

3 Mortem Blood concentrations are times greater than antemor- The study reported here examines three cases in which ante- tem concentrations. Furthermore, as both Methamphetamine and mortem specimens were collected and Postmortem peripheral amphetamine have previously been shown to have liver/peripheral Blood specimens were also available. This study presents an in- Blood (L/P) ratios of 5 8, it can be proposed that drugs displaying L/P vestigation of PMR, and provides better insight on the extent to ratios ranging from 5 to 10 may exhibit Postmortem concentrations up which Methamphetamine and amphetamine concentrations to twice those concentrations circulating in Blood before death. may be expected to increase after death as a result of PMR. Introduction Methamphetamine is a highly addictive central nervous system Methods stimulant that can be injected, snorted, smoked or ingested Cases orally.

4 Although available by prescription for the treatment of attention-de cit disorder (1), the major use (abuse) of metham- Case 1. phetamine remains illicit generally synthesized in clandestine This 44-year-old man had no reported medical history. On the laboratories. It is metabolized by N-demethylation to amphet- day of his death, he was with his girlfriend playing video games amine, which is also a pharmacologically active drug (2). when he suddenly grabbed his chest and became unresponsive. Single oral doses of Methamphetamine have been reported to Bystander cardiopulmonary resuscitation (CPR) was initiated. He produce peak plasma concentrations up to mg/L with a was transported by ground ambulance to a nearby hospital with mg dose (3). A 30 mg oral dose resulted in an average peak an estimated down time of 35 min. He arrived in the emergency serum Methamphetamine concentration of mg/L (range room with CPR in progress with ventricular brillation.)

5 Despite mg/L) (4). Single intravenous doses ( mg/kg) administration of multiple cardiac medications, including epi- have resulted in an average peak plasma Methamphetamine con- nephrine, lidocaine and amiodarone, and de brillation attempts, centration of mg/L, with amphetamine at mg/L he died in the emergency room. His girlfriend later admitted (5). Half-life of elimination is pH dependent, ranging from 6 to that they had been using Methamphetamine . The autopsy docu- 15 h for Methamphetamine and 7 to 34 h for amphetamine (2). mented ndings of hypertensive and atherosclerotic cardiovas- Blood concentrations ranging from to mg/L have cular disease. The heart was enlarged (580 g) with concentric been reported in Methamphetamine abusers showing violent and left ventricular hypertrophy. The coronary arteries demon- irrational behavior (6) and from to mg/L in individuals strated focal, moderate to marked calci c atherosclerotic sten- arrested for erratic driving (7).

6 Postmortem Blood concentrations osis of the vessel lumens. Microscopic examination of the heart have been described to range from to 13 mg/L in abusers muscle documented both acute cardiomyocyte necrosis and ex- who died of traumatic injury by violent means (8). Deaths tensive areas of older brosis. toxicology testing con rmed only resulting from overdose have been shown with methampheta- Methamphetamine . The cause of death was listed as hyperten- mine concentrations ranging from to 18 mg/L, with an sive and atherosclerotic cardiovascular disease with acute meth- average of mg/L (9). When attempting to compare Blood and amphetamine intoxication contributing. Autopsy was performed clinical plasma/serum concentrations, it is important to be h after death. Antemortem Blood specimens were drawn aware that the Blood /plasma ratio for Methamphetamine is 22 min prior to pronouncement of death.

7 (2). The distribution of Methamphetamine and amphetamine Case 2. in Postmortem peripheral Blood , central Blood and liver has This 46-year-old man was the unrestrained rear seat passenger of been recently reported (10). Methamphetamine central a pickup truck traveling on an interstate when it veered off the # The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: CG 069_V1 Antemortem & Postmortem Methamphetamine Blood Concentrations Page 1 of 31. road and went down a center embankment, rolling over. He was Methamphetamine /amphetamine con rmation partially ejected. Witnesses found him initially responsive and yelling. He was transported by ground to a nearby location for Materials airlift, but lost his pulse while being loaded onto the helicopter. Solvents (dichloromethane, methanol, ethyl acetate, isopropanol He arrived at a regional trauma center with resuscitative efforts and acetone) were EMD Chemicals OmniSolvw grade, purchased still underway.

8 Despite resuscitative efforts, death was pro- from VWR International (Radnor, PA). Penta uoropropionic an- nounced almost 2 h following the initial report of the incident. hydride (PFPA) was obtained from Sigma-Aldrich (St. Louis, MO). The decedent's medical history included bromyalgia, chronic Ammonium hydroxide (ACS) and glacial acetic acid (ACS) were fatigue and Methamphetamine use. toxicology testing con- obtained from VWR International. Zinc sulfate heptahydrate rmed Methamphetamine and cannabinoids (which were not (Certi ed ACS) was obtained from Fisher Scienti c (Pittsburg, quanti ed). The autopsy documented multiple bone fractures PA), and anhydrous sodium acetate (GR ACS Mallinckrodt) was and visceral lacerations, and the cause of death was listed as mul- obtained from VWR, Inc. Methamphetamine , amphetamine, tiple blunt force injuries.

9 Autopsy was performed h after Methamphetamine -D5 and amphetamine-D5 were obtained from death. Antemortem Blood specimens were drawn 7 min prior to Downloaded from by guest on 24 May 2019. Cerilliant (Austin, TX). Solid-phase extraction (SPE) columns pronouncement of death. were Trace-Bw from SPEWare Corp. (Baldwin Park, CA). Aqueous working standards containing mg/L each of Methamphetamine and amphetamine and internal standards Case 3 containing mg/L each of Methamphetamine -D5 and amphet- This 37-year-old male had a history of drug and alcohol abuse. amine-D5 were prepared. Linear calibration curves from to On the day of his death, he developed erratic and bizarre behav- mg/L produced using ve calibrators ( , , , and ior after consuming alcohol. While being taken to a regional hos- mg/L) were made by diluting the working standard.

10 All calibra- pital in a private passenger vehicle, he became unresponsive. On tors were prepared in deionized water. A commercial whole - Blood arrival, he had agonal breathing, but no heartbeat. Death was pro- toxicology control containing mg/L of Methamphetamine nounced after resuscitative efforts in the emergency room. and amphetamine obtained from UTAK Laboratories, Inc. toxicology testing con rmed alcohol ( ) and metham- (Valencia, CA) (Product #98818), and an in-house whole - Blood phetamine; gastric contents contained 15 mg of methampheta- control containing mg/L of Methamphetamine and amphet- mine. The autopsy documented an empty, small, sealable plastic amine (prepared from a second source of drug stock) were run bag in the gastric contents, indicating ingestion of a baggie of with each batch of calibrators and cases.