Hill D W, Hyde W G, Kind A J, Greulich D, Hopkins S
Pathobiology Department, University of Connecticut, Storrs 06269, USA.
J Anal Toxicol. 2000 May-Jun;24(4):281-8. doi: 10.1093/jat/24.4.281.
Aramine (metaraminol bitartrate) has been found in the possession of horse trainers and veterinarians who have been investigated for possible inappropriate drug administration to racing horses. Metaraminol (3-hydroxyphenylisopropanolamine) is a sympathomimetic amine that directly and indirectly affects adrenergic receptors, with alpha effects being predominant. Because it has the potential to affect the performance of a racing horse, its use is prohibited. In the present study, methods for the detection of metaraminol were developed. Metaraminol was found to be extracted with poor recovery (< 50%) from aqueous solutions by routine basic extraction or cation exchange/reversed-phase solid-phase extraction techniques. However, an extractive acetylation method gave good (> 90%) recovery of metaraminol from aqueous samples. Sequential urine samples collected from horses administered metaraminol intramuscularly at 0.02, 0.10, and 0.23 mg/kg were extracted by the developed extractive acetylation procedure and analyzed by gas chromatography-mass spectrometry (GC-MS) in full-scan and selected ion monitoring modes. Norphenylephrine was used as an internal standard for quantitative analysis. The maximum concentration of metaraminol occurred between 1 and 2 h postadministration. Metaraminol was detected in the 0.23 mg/kg administration urine for 24 h postadministration. Metaraminol was detected for the 0.10 and 0.02 mg/kg doses for approximately 8 h postadministration. No apparent biotransformation products were observed in a reaction mixture of metaraminol and horse liver microsomal reaction mixture. Comparison of gas chromatograms of the extracts of the postadministration urine samples with those of the pre-administration samples failed to reveal any exogenous compound other than metaraminol.
在对可能向赛马不当用药展开调查时，发现驯马师和兽医持有阿拉明（重酒石酸间羟胺）。间羟胺（3 - 羟基苯异丙醇胺）是一种拟交感神经胺，可直接和间接影响肾上腺素能受体，其中以α效应为主。因其有可能影响赛马的表现，故禁止使用。在本研究中，开发了检测间羟胺的方法。结果发现，通过常规碱性萃取或阳离子交换/反相固相萃取技术从水溶液中萃取间羟胺时回收率较低（<50%）。然而，萃取乙酰化方法从水性样品中回收间羟胺的效果良好（>90%）。对分别以0.02、0.10和0.23 mg/kg肌肉注射间羟胺的马匹采集的连续尿液样本，采用开发的萃取乙酰化程序进行萃取，并通过气相色谱 - 质谱联用仪（GC - MS）在全扫描和选择离子监测模式下进行分析。去甲肾上腺素用作定量分析的内标。间羟胺的最大浓度出现在给药后1至2小时之间。在给药后24小时内，在0.23 mg/kg给药剂量的尿液中检测到了间羟胺。在给药后约8小时内，检测到了0.10和0.02 mg/kg剂量的间羟胺。在间羟胺与马肝微粒体反应混合物的反应体系中未观察到明显的生物转化产物。将给药后尿液样本提取物的气相色谱图与给药前样本的气相色谱图进行比较，除间羟胺外未发现任何外源性化合物。
