Sandbaumhüter Friederike A, Theurillat Regula, Thormann Wolfgang
Clinical Pharmacology Laboratory, University of Bern, Bern, Switzerland.
Electrophoresis. 2017 Aug;38(15):1878-1885. doi: 10.1002/elps.201700016. Epub 2017 Mar 9.
The racemic N-methyl-d-aspartate receptor antagonist ketamine is used in anesthesia, analgesia and the treatment of depressive disorders. It is known that interactions of hydroxylated norketamine metabolites and 5,6-dehydronorketamine (DHNK) with the α -nicotinic acetylcholine receptor and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor are responsible for the antidepressive effects. Ketamine and its first metabolite norketamine are not active on these receptors. As stereoselectivity plays a role in ketamine metabolism, a cationic capillary electrophoresis based method capable of resolving and analyzing the stereoisomers of four hydroxylated norketamine metabolites, norketamine and DHNK was developed. The assay is based on liquid/liquid extraction of the analytes from the biological matrix, electrokinetic sample injection across a buffer plug and analysis of the stereoisomers in a phosphate background electrolyte (BGE) at pH 3 comprising a mixture of sulfated β-cyclodextrin (5 mg/mL) and highly sulfated γ-cyclodextrin (0.1%). The method was used to analyze samples of an in vitro study in which ketamine was incubated with equine liver microsomes and in plasma samples of dogs and horses that were collected after an i.v. bolus injection of racemic ketamine.
消旋N-甲基-D-天冬氨酸受体拮抗剂氯胺酮用于麻醉、镇痛及抑郁症治疗。已知羟基化去甲氯胺酮代谢物和5,6-脱氢去甲氯胺酮（DHNK）与α-烟碱型乙酰胆碱受体及α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体的相互作用是其抗抑郁作用的原因。氯胺酮及其首个代谢物去甲氯胺酮对这些受体无活性。由于立体选择性在氯胺酮代谢中起作用，因此开发了一种基于阳离子毛细管电泳的方法，该方法能够分离并分析四种羟基化去甲氯胺酮代谢物、去甲氯胺酮和DHNK的立体异构体。该测定法基于从生物基质中液/液萃取分析物，通过缓冲塞进行电动进样，并在pH 3的磷酸盐背景电解质（BGE）中分析立体异构体，该电解质包含硫酸化β-环糊精（5 mg/mL）和高硫酸化γ-环糊精（0.1%）的混合物。该方法用于分析体外研究的样本，在该研究中氯胺酮与马肝微粒体一起孵育，并用于分析静脉推注消旋氯胺酮后采集的犬和马的血浆样本。
