Morrison Lucas M, Unger Kirk A, Watterson James H
Department of Forensic Science, Laurentian University, 935 Ramsey Lake Road, Sudbury, Ontario, Canada P3E 2C6.
J Anal Toxicol. 2017 Jul 1;41(6):566-572. doi: 10.1093/jat/bkx040.
Analysis of dextromethorphan (DXM) and its metabolite dextrorphan (DXT) in skeletal remains of rats following acute (ACU, 75 mg/kg, IP, n = 10) or three repeated (REP, 25 mg/kg, IP, n = 10, 40-min interval) doses of DXM is described. Following dosing and euthanasia, rats decomposed outdoors to skeleton in two different microclimate environments (n = 5 ACU and n = 5 REP at each site): Site A (shaded forest microenvironment) and Site B (rocky substrate exposed to direct sunlight, 600 m from Site A). Two drug-free rats at each site served as negative controls. Skeletal elements (vertebrae, ribs, pelvic girdles, femora, tibiae, skulls and scapulae) were recovered, pulverized and underwent methanolic microwave assisted extraction (MAE). Extracts were analyzed by GC-MS following clean-up by solid-phase extraction (SPE). Drug levels, expressed as mass-normalized response ratios and the ratios of DXT and DXM levels (RRDXT/RRDXM) were compared between drug exposures, microclimate sites, and across skeletal elements. DXM levels differed significantly (P < 0.05) between corresponding bone elements across exposure groups (5/7-site A; 4/7-site B), but no significant differences in DXT levels were observed between corresponding elements. RRDXT/RRDXM differed significantly (P < 0.05) between corresponding bone elements across exposure groups (6/7-site A; 5/7-site B). No significant differences were observed in levels of DXM, DXT or RRDXT/RRDXM between corresponding elements from either group between sites. When data from all bone elements was pooled, levels of DXM and RRDXT/RRDXM differed significantly between exposure groups at each site, while those of DXT did not. For both exposure groups, comparison of pooled data between sites showed no significant differences in levels of DXM, DXT or RRDXT/RRDXM. Different decomposition microclimates did not impede the discrimination of DXM exposure patterns from the analyses of DXM, DXT and RRDXT/RRDXM in bone samples.
描述了对大鼠急性（ACU，75毫克/千克，腹腔注射，n = 10）或三次重复（REP，25毫克/千克，腹腔注射，n = 10，间隔40分钟）给予右美沙芬（DXM）后其骨骼残骸中右美沙芬（DXM）及其代谢物右啡烷（DXT）的分析。给药并安乐死后，大鼠在两种不同的微气候环境中于户外分解为骨骼（每个地点ACU组n = 5只，REP组n = 5只）：地点A（阴凉的森林微环境）和地点B（暴露于直射阳光下的岩石基质，距地点A 600米）。每个地点的两只无药物大鼠作为阴性对照。回收骨骼元素（椎骨、肋骨、骨盆带、股骨、胫骨、头骨和肩胛骨），粉碎后进行甲醇微波辅助萃取（MAE）。萃取物经固相萃取（SPE）净化后用气相色谱-质谱联用仪（GC-MS）分析。比较了不同药物暴露组、微气候地点以及不同骨骼元素之间的药物水平，以质量归一化响应比以及DXT和DXM水平之比（RRDXT/RRDXM）表示。各暴露组相应骨元素之间的DXM水平存在显著差异（P < 0.05）（地点A为5/7；地点B为4/7），但相应元素之间未观察到DXT水平有显著差异。各暴露组相应骨元素之间的RRDXT/RRDXM存在显著差异（P < 0.05）（地点A为6/7；地点B为5/7）。两个地点相应组的相应元素之间，DXM、DXT或RRDXT/RRDXM水平未观察到显著差异。当汇总所有骨元素的数据时，每个地点不同暴露组之间的DXM和RRDXT/RRDXM水平存在显著差异，而DXT水平则无差异。对于两个暴露组，比较地点之间的汇总数据表明，DXM、DXT或RRDXT/RRDXM水平无显著差异。不同的分解微气候并未妨碍通过对骨样本中DXM、DXT和RRDXT/RRDXM的分析来区分DXM暴露模式。
