Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.
Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia, USA.
J Sep Sci. 2023 Nov;46(22):e2300395. doi: 10.1002/jssc.202300395. Epub 2023 Sep 8.
Interest has increased in the role of N-acyl amino acids in a variety of disease states and as potential pharmacotherapies. Recently, N-oleoyl glycine and N-oleoyl alanine have shown promise in reducing the rewarding effects of drugs of abuse and alleviating withdrawal signs in rodent models. Previously published methods for the quantitation of these analytes by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in tissue were part of extensive lipidomic panels which may result in limited sensitivity and selectivity and also reported low recovery. Presented is a method for the extraction and HPLC-MS/MS analysis of N-oleoyl glycine and N-oleoyl alanine. The bias and precision of the assay were determined to be within ± 20%. The method was shown to be reliable and robust, with over 90% recovery for the low-level analytes. Increasing concentrations of N-oleoyl glycine and N-oleoyl alanine were quantitated in mouse brain and plasma following exogenous administration. This method was developed to serve to support studies investigating the pharmacokinetics and involvement of N-oleoyl glycine and N-oleoyl alanine in drug dependence and other diseases.
人们对 N-酰基氨基酸在各种疾病状态中的作用以及作为潜在的药物治疗方法越来越感兴趣。最近，N-油酰甘氨酸和 N-油酰丙氨酸在减少滥用药物的奖赏效应和缓解啮齿动物模型的戒断症状方面显示出了希望。以前发表的通过高效液相色谱-串联质谱法（HPLC-MS/MS）在组织中定量这些分析物的方法是广泛脂质组学分析的一部分，这可能导致灵敏度和选择性有限，并且报告的回收率也很低。本研究提出了一种用于提取和 HPLC-MS/MS 分析 N-油酰甘氨酸和 N-油酰丙氨酸的方法。该测定的偏差和精密度被确定在±20%范围内。该方法被证明是可靠和稳健的，对于低水平的分析物回收率超过 90%。在外源性给药后，可定量检测小鼠脑和血浆中 N-油酰甘氨酸和 N-油酰丙氨酸的浓度增加。该方法旨在支持研究 N-油酰甘氨酸和 N-油酰丙氨酸在药物依赖和其他疾病中的药代动力学和作用。
