Influence of dose-death interval on colchicine and metabolite distribution in decomposed skeletal tissues

详细信息    查看全文

• 作者：Anic B. Imfeld ; James H. Watterson
• 关键词：Forensic toxicology ; Bone ; Colchicine ; Microwave assisted extraction ; UHPLC
• 刊名：International Journal of Legal Medicine
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：130
• 期：2
• 页码：371-379
• 全文大小：1,268 KB
• 参考文献：1.McIntyre IM, King CV, Boratto M, Drummer OH (2000) Post-mortem drug analyses in bone and bone marrow. Ther Drug Monit 22:79–83CrossRef PubMed
  2.McGrath KK, Jenkins AJ (2009) Detection of drugs of forensic importance in postmortem bone. Am J Forensic Med Pathol 30(1):40–44CrossRef PubMed
  3.Watterson JH, Desrosiers NA, Betit CC, Dean D, Wyman JF (2010) Relative distribution of drugs in decomposed skeletal tissue. J Anal Toxicol 34:510–515CrossRef PubMed
  4.Watterson JH, Cornthwaite HM (2013) Discrimination between patterns of drug exposure by toxicological analysis of decomposed skeletal tissues, part II: amitriptyline and citalopram. J Anal Toxicol 37:565–572CrossRef PubMed
  5.Watterson JH, Desrosiers NA (2011) Examination of the effect of dose-death interval on detection of meperidine exposure in decomposed skeletal tissues using microwave-assisted extraction. Forensic Sci Int 207:40–45CrossRef PubMed
  6.Delabarde T, Keyser C, Tracqui A, Charabidze D, Ludes B (2013) The potential of forensic analysis on human bones found in a riverine environment. Forensic Sci Int 228:e1–e5CrossRef PubMed
  7.Vardakou I, Athanaselis S, Pistos C, Papadodima S, Spiliopoulou C, Moraitis K (2014) The clavicle bone as an alternative matrix in forensic toxicological analysis. J Forensic Legal Med 22:7–9CrossRef
  8.Watterson JH, Donohue JP, Betit CC (2012) Comparison of relative distribution of ketamine and norketamine in decomposed skeletal tissues following single and repeated exposures. J Anal Toxicol 36(6):429–433CrossRef PubMed
  9.Wiebe TR, Watterson JH (2014) Analysis of tramadol and O-desmethyltramadol in decomposed skeletal tissues following acute and repeated tramadol exposure by gas chromatography mass spectrometry. Forensic Sci Int 242:261–265CrossRef PubMed
  10.Watterson JH, Imfeld AI, Cornthwaite HM (2014) Determination of colchicine and O-demethylated metabolites in decomposed skeletal tissues by microwave assisted extraction, microplate solid phase extraction and ultra-high performance liquid chromatography (MAE-MPSPE-UHPLC). J Chromatogr B 960:145–150CrossRef
  11.Rochdi M, Sabouraud A, Baud FJ, Bismuth C, Scherrmann JM (1992) Toxicokinetics of colchicine in humans: analysis of tissue, plasma and urine data in ten cases. Hum Exp Toxicol 11:510–516CrossRef PubMed
  12.Leighton JA, Bay MK, Maldonado AL, Johnson RF, Schenker S, Speeg KV (1990) The effect of liver dysfunction on colchicine pharmacokinetics in the rat. Hepatology 11:210–215CrossRef PubMed
  
• 作者单位：Anic B. Imfeld (1)
  James H. Watterson (1)
  
  1. Department of Forensic Science, Laurentian University, 935 Ramsey Lake Rd, Sudbury, ON, Canada, P3E 2C6
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Forensic Medicine
  Medical Law
  Medicine/Public Health, general
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1437-1596

文摘

The semi-quantitative analysis of decomposed bone of rats exposed to colchicine and euthanized following different time intervals postexposure (i.e., dose-death interval, DDI) is described. Rats received colchicine (50 mg/kg, i.p.) and were euthanized 30 min (DDI1; n = 4), 60 min (DDI2; n = 4), or 180 min (DDI3; n = 4) postdose. Drug-free animals (n = 3) served as negative controls. Perimortem heart plasma was collected. Remains were decomposed to skeleton outdoors and then collected and sorted (skull, vertebrae, rib, pelvis, femur, tibia). Bones were dried, pulverized, and prepared by microwave-assisted extraction and microplate solid-phase extraction (MAE-MPSPE), followed by analysis for colchicine, 3-demethylcolchicine (3DMC), and 2-demethylcolchicine (2DMC) by ultra-high-performance liquid chromatography with photodiode array detection (UHPLC-PDA) at 350 nm. Bone type was a main effect (Kruskall-Wallis, p < 0.05) with respect to drug level (expressed as mass-normalized response ratio, RR/m) for each analyte, at each DDI. For all samples, DDI was a main effect (Kruskall-Wallis, p < 0.05) with respect to analyte level, and the ratio of analyte levels (RR_3DMC/RR_COLCH, RR_2DMC/RR_COLCH, and RR_2DMC/RR_3DMC). Bone COLCH levels varied by 19-fold, 12-fold, and 60-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Bone 3DMC levels varied by 12-fold, 11-fold and 17-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Bone 2DMC levels varied by 20-fold, 14-fold, and 14-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Values of RR_3DMC/RR_COLCH varied by 16-fold, 5-fold, and 5-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Values of RR_2DMC/RR_COLCH varied by 10-fold, 6-fold, and 12-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Values of RR_2DMC/RR_3DMC varied by 3-fold, 5-fold, and 2-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Measured analyte levels in bone correlated poorly with corresponding levels in blood (r = −0.65–+0.31). Measured values of RR_2DMC/RR_COLCH and RR_2DMC/RR_3DMC in bone also correlated poorly with corresponding values in blood. Measured values of RR_3DMC/RR_COLCH were well correlated with corresponding blood levels for all bone types except skull (r = 0.91–0.97).