Protein binding of ketamine and its active metabolites to human serum
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
Authors: Hijazi, Y; Boulieu, R
Abstract
Ketamine is an anaesthetic agent extensively used in intensive care patients, and it has proved its efficacy in the management of burned patients. In these patients, alterations in serum protein binding occur that may have significant clinical implications. Scarce data were observed in the literature about the binding of ketamine to human plasma proteins, and no data about the binding of its active metabolites, norketamine (NK) and dehydronorketamine (DHNK) were found. In this study, protein binding of ketamine, NK and DHNK in human serum were determined using the ultrafiltration technique. The percentage of drug bound to serum proteins at 30degreesC was found to be 69%, 60% and 50% for DHNK, ketamine and NK, respectively, while these percentages were 75%, 64% and 54% for DHNK, ketamine and NK respectively at 20degreesC. The binding of ketamine and its metabolites was independent of drug concentration.
GC-MS quantification of ketamine, norketamine, and dehydronorketamine in urine specimens and comparative study using ELISA as the preliminary test methodology
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
Authors: Cheng, Pai-Sheng; Fu, Chien-Yu; Lee, Choung-Huei; Liu, Chiareiy; Chien, Chun-Sheng
Abstract
An automated solid-phase extraction procedure combined with the gas chromatography-mass spectrometry (GC-MS) methodology, without derivatization, has been developed for the determination of ketamine (K), norketamine (NK), and dehydronorketamine (DHNK) in urine. The analytical approach is simple and rapid, yet reliable, achieving good linearity (r(2) > 0.999 over the concentration range of 30 to 1000 ng/mL), sensitivity (limits of quantification= 15, 10, and 20ng/mL for K, NK, and DHNK, respectively), accuracy (90-104%), and precision (RSD < 8.1%) for all analytes. Two hundred and six urine specimens collected from suspected drug users were analyzed by this protocol and also screened by Neogen ELISA method to evaluate the efficiency as well as the compatibility of these two methods. Neogen ELISA showed high efficiency (98.1%), high sensitivity (90.9%), high specificity (98.9%), low false-positive rate (1.1%), and moderate false-negative rate (9.1%), adopting 10 ng/mL K as the cutoff. Neogen ELISA screening followed by GC-MS analysis appeared to be a good screening-confirmation test scheme for the analysis of K in urine. Twenty of the 22 positive urine specimens contained all three analytes simultaneously, with DHNK showing the highest and K the lowest concentrations. (c) 2007 Elsevier B.V. All rights reserved.
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