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LC-MS/MS analysis of pholedrine in a fatal intoxication case.
Forensic Sci Int. 2003 Apr 23; 133(1-2):101-6.FS

Abstract

Pholedrine (4'-hydroxymethamphetamine) is a cardiovascular agent exerting hypertensive and adrenergic effects. High doses may cause a drop in the peripheral circulation blood flow and increase blood pressure, heart rate and body temperature up to a state of central respiratory paralysis. A 15-year-old girl who suffered from heavy agitation and hallucinations was admitted to the intensive care unit in a comatose state. The clinical findings included a maximum heart rate of 170 bpm and a body temperature of 43.8 degrees C. Resuscitation measures were in vain and abandoned after approximately 2h. A toxicological emergency analysis using GC/MS revealed a considerable amount of pholedrine in blood and urine. A method for determining pholedrine in human body fluids utilizing high-performance liquid chromatography (HPLC)/tandem mass spectrometry (LC-MS/MS) with a turbo ion-spray source was developed, using D11-methamphetamine and D5-methylenedioxymethamphetamine as internal standards. Samples were prepared by SPE extraction using SPEC-C18AR/MP3((R)) columns, which yielded the best extraction recovery (67%). Chromatographic separation was achieved at pH 5 on an RP-18 stationary phase applying gradient elution from 50 to 70% of B (methanol/acetonitrile 3/1 (v/v), 0.02% acetic acid) in A (5mM ammonium acetate/acetonitrile 95/5 (v/v), 0.02% acetic acid). Supra-pure acetic acid was added to the post-column effluent with a flow rate of 0.2 microl/min to optimize ionization. Detection was carried out in the positive ionization, multiple reaction monitoring (MRM) mode. The chromatograms showed no interference from other substances. The limit of detection (LOD, S/N=3) of pholedrine was 0.8 ng/ml and its lower limit of quantification (LLOQ, S/N=10) 3ng/ml. The calibration curve was linear (r=0.999) in the range 1-100 ng/ml. Samples with higher concentrations were diluted to suit the working range. The intra-day R.S.D. between 5 and 80 ng/ml were 3.8-8.7% and the inter-day R.S.D. between 5 and 100 ng/ml were 6.7-10.7%. The pholedrine concentrations in blood and urine collected when the girl was still alive were 16.1 microg/ml (R.S.D. 10.5%) and 1120 microg/ml (R.S.D. 8%), respectively. In post-mortem samples, they were 23.0 microg/ml (R.S.D. 5.1%) in heart blood and 27.3 microg/g (R.S.D. 6.6%) in the liver.

Authors+Show Affiliations

Institute of Forensic Medicine, University Hospital, Leipziger Strasse 44, 39120 Magdeburg, Germany. wolfgang.roemhild@medizin.uni-magdeburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Comparative Study
Journal Article

Language

eng

PubMed ID

12742695

Citation

Römhild, W, et al. "LC-MS/MS Analysis of Pholedrine in a Fatal Intoxication Case." Forensic Science International, vol. 133, no. 1-2, 2003, pp. 101-6.
Römhild W, Krause D, Bartels H, et al. LC-MS/MS analysis of pholedrine in a fatal intoxication case. Forensic Sci Int. 2003;133(1-2):101-6.
Römhild, W., Krause, D., Bartels, H., Ghanem, A., Schöning, R., & Wittig, H. (2003). LC-MS/MS analysis of pholedrine in a fatal intoxication case. Forensic Science International, 133(1-2), 101-6.
Römhild W, et al. LC-MS/MS Analysis of Pholedrine in a Fatal Intoxication Case. Forensic Sci Int. 2003 Apr 23;133(1-2):101-6. PubMed PMID: 12742695.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LC-MS/MS analysis of pholedrine in a fatal intoxication case. AU - Römhild,W, AU - Krause,D, AU - Bartels,H, AU - Ghanem,A, AU - Schöning,R, AU - Wittig,H, PY - 2003/5/14/pubmed PY - 2003/7/30/medline PY - 2003/5/14/entrez SP - 101 EP - 6 JF - Forensic science international JO - Forensic Sci. Int. VL - 133 IS - 1-2 N2 - Pholedrine (4'-hydroxymethamphetamine) is a cardiovascular agent exerting hypertensive and adrenergic effects. High doses may cause a drop in the peripheral circulation blood flow and increase blood pressure, heart rate and body temperature up to a state of central respiratory paralysis. A 15-year-old girl who suffered from heavy agitation and hallucinations was admitted to the intensive care unit in a comatose state. The clinical findings included a maximum heart rate of 170 bpm and a body temperature of 43.8 degrees C. Resuscitation measures were in vain and abandoned after approximately 2h. A toxicological emergency analysis using GC/MS revealed a considerable amount of pholedrine in blood and urine. A method for determining pholedrine in human body fluids utilizing high-performance liquid chromatography (HPLC)/tandem mass spectrometry (LC-MS/MS) with a turbo ion-spray source was developed, using D11-methamphetamine and D5-methylenedioxymethamphetamine as internal standards. Samples were prepared by SPE extraction using SPEC-C18AR/MP3((R)) columns, which yielded the best extraction recovery (67%). Chromatographic separation was achieved at pH 5 on an RP-18 stationary phase applying gradient elution from 50 to 70% of B (methanol/acetonitrile 3/1 (v/v), 0.02% acetic acid) in A (5mM ammonium acetate/acetonitrile 95/5 (v/v), 0.02% acetic acid). Supra-pure acetic acid was added to the post-column effluent with a flow rate of 0.2 microl/min to optimize ionization. Detection was carried out in the positive ionization, multiple reaction monitoring (MRM) mode. The chromatograms showed no interference from other substances. The limit of detection (LOD, S/N=3) of pholedrine was 0.8 ng/ml and its lower limit of quantification (LLOQ, S/N=10) 3ng/ml. The calibration curve was linear (r=0.999) in the range 1-100 ng/ml. Samples with higher concentrations were diluted to suit the working range. The intra-day R.S.D. between 5 and 80 ng/ml were 3.8-8.7% and the inter-day R.S.D. between 5 and 100 ng/ml were 6.7-10.7%. The pholedrine concentrations in blood and urine collected when the girl was still alive were 16.1 microg/ml (R.S.D. 10.5%) and 1120 microg/ml (R.S.D. 8%), respectively. In post-mortem samples, they were 23.0 microg/ml (R.S.D. 5.1%) in heart blood and 27.3 microg/g (R.S.D. 6.6%) in the liver. SN - 0379-0738 UR - https://www.unboundmedicine.com/medline/citation/12742695/LC_MS/MS_analysis_of_pholedrine_in_a_fatal_intoxication_case_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0379073803000550 DB - PRIME DP - Unbound Medicine ER -