Tandem mass spectrometry for the trace determination of tryptolines in crude brain extracts.
Tandem mass spectrometry for the trace determination of tryptolines in crude brain extracts.
复制标题
串联质谱法用于粗脑提取物中痕量测定色氨酸。
DOI：
10.1021/ac00273a027
复制
发表时间：
1984
影响因子：
7.4
通讯作者：
Faull,KF
中科院分区：
文献类型：
--
作者：
Johnson,JV;Yost,RA;Faull,KF
在哺乳动物组织中自然存在的色氨酸（1,2,3,4 -四氢-/3-碳酮）是一个有争议的主题。这是由于用于鉴定的方法缺乏特异性，以及在样品纯化过程中可能形成虚假。串联质谱（MS/MS）由于其高灵敏度和固有的选择性，已被证明是一种强有力的混合物分析工具。本文报道了一种三重四极柱GC/MS/MS技术，用于色氨酸的七氟丁基衍生物的测定。比较了短填充柱和18 m键合相熔融石英柱的正负化学电离（Cl）和选择性离子和选择性反应监测（SIM和SRM）。采用毛细管柱测定了色氨酸七氟丁基衍生物在CI-SIM阴性、CI-SRM阴性、CI-SIM阳性和CI-SRM阳性条件下的检出限分别为0.5、0.2、19和60 pg。虽然两种阴性Cl技术具有相似的检测限，但阴性CI-SRM的更高选择性使其成为分析粗脑提取物的首选技术。色氨酸（四氢-0-碳碱，表1）是一类由吲哚胺和醛之间的Pictet-Spengler缩合反应产生的化合物。对这些化合物的生理意义的兴趣有三个来源。首先，生理条件下体外的缩合反应容易进行（1,2），这引发了人们的猜测，即这些化合物可能在哺乳动物组织中自然存在。色氨酸的神经药理学作用（3-5）进一步证实了这一推测，认为这种化合物在体内的存在可能对脑神经传递的调节具有重要意义(6)。其次，也有人推测这些化合物的体内形成可能与酒精滥用综合征有关(7)。其基础是乙醛是乙醇的主要代谢物。饮酒后，血浆中乙醛浓度增加(8)，从而增加了乙醛-吲哚胺缩合反应的可能性。这一假设得到了一些实验的支持，这些实验表明，当向老鼠大脑注射色氨酸时，它们更喜欢喝酒而不是喝水（9,10）。第三，对这类化合物的兴趣也源于它们在脑膜制剂中取代苯二氮卓受体的氚化地西泮的能力的报道（11-13）。这些报道引起了人们的猜测，这类化合物可能是苯二氮卓类受体的内源性配体。
The natural occurrence of tryptolines (1, 2, 3, 4-tetrahydro-/3-carbollnes) In mammalian tissue Is the subject of controversy. This Is due to the lack of specificity In the methods used for Identification and the possibility of artlfactual formation during sample purification. Tandem mass spectrometry (MS/MS) has been shown to be a powerful tool for mixture analysis due to Its high sensitivity and Inherent selectivity. Here we report a triple quadrupole GC/MS/MS technique for the determination of the heptafluorobutyryl derivatives of the tryptolines. Comparisons were made between positive and negative chemical Ionization (Cl) and between selected Ion and se-lected reaction monitoring (SIM and SRM) with a short packed column and an 18-m bonded-phase fused silica ca-pillary column. By use of the capillary column, the limits of detection of the heptafluorobutyryl derivative of tryptoline were determined to be 0.5, 0.2, 19, and 60 pg for negative CI-SIM, negative CI-SRM, positive CI-SIM, and positive CI-SRM, respectively. Although the two negative Cl tech-niques have similar limits of detection, the greater selectivity of the negative CI-SRM made It the preferred technique for the analysis of crude brain extracts.The tryptolines (tetrahydro-0-carbolines, Table I) are the class of compounds which arise from the Pictet-Spengler condensation reactions between indoleamines and aldehydes. Interest in the physiological significance of these compounds stems from three sources. Firstly, the ease with whichthe condensation reaction proceeds invitro under physiological conditions (1, 2) has initiated speculation that the compounds could occur naturally in mammalian tissues. The neuro-pharmacological effects of tryptolines (3-5) have added to this speculation by prompting the suggestion that the in vivo presence of such compounds could have important implica-tions for the regulation of cerebral neurotransmission (6). Secondly, there has also been speculation that the in vivo formation of these compounds could be related to the alco-hol-abuse syndrome (7). The basis for this stems from the fact that acetaldehyde is a major metabolite of ethyl alcohol. Plasma concentrations of the acetaldehyde increase following alcohol consumption (8), thus increasing the likelihood of acetaldehyde-indoleamine condensation reactions. This hypothesis has gained sensational but controversial support from experiments in which rats preferredto drink alcohol over water when tryptolines were injected into their brains (9, 10). Thirdly, interest in this class of compounds has also stemmed from reports of their ability to displace tritiated diazepam from the benzodiazepine receptor in brain membrane preparations (11-13). These reports have given rise to speculation that a compound of this class could be an endogenous ligand for the benzodiazepine receptor.