Rapid electrophoretic monitoring of the anaesthetic ketamine and its metabolite norketamine in rat blood using a contactless conductivity detector to study the pharmacokinetics

Abstract

A method of capillary electrophoresis with contactless conductivity detection has been developed for non-enantioselective monitoring the anaesthetic ketamine and its main metabolite norketamine. The separation is performed in a 15 μm capillary with an overall length of 31.5 cm and length to detector of 18 cm; inner surface of the capillary is covered with a commercial coating solution to reduce the electroosmotic flow. In an optimised background electrolyte with composition 2 M acetic acid + 1% v/v coating solution under application of a high voltage of 30 kV, the migration time is 97.1 s for ketamine and 95.8 s for norketamine, with an electrophoretic resolution of 1.2. The attained detection limit was 83 ng/mL (0.3 μmol/L) for ketamine and 75 ng/mL (0.3 μmol/L) for norketamine; the number of theoretic plates for separation of an equimolar model mixture with a concentration of 2 μg/mL was 683 500 plates/m for ketamine and 695 400 plates/m for norketamine. Laboratory preparation of rat blood plasma is based on mixing 10 μL of plasma with 30 μL of acidified acetonitrile, followed by centrifugation. A pharmacokinetic study demonstrated an exponential decrease in the plasma concentration of ketamine after intravenous application and much slower kinetics for intraperitoneal application. K E Y W O R D Sacetonitrile stacking, capillary electrophoresis, contactless conductivity detection, ketamine, pharmacokinetics 2062

Electrophoretic Determination of Symmetric and Asymmetric Dimethylarginine in Human Blood Plasma with Whole Capillary Sample Injection

“…Venous blood samples were collected in test tubes containing EDTA and, after initial treatment, the separated plasma samples were stored in a freezer at −80 • C until the analysis. Before the CE measurement, 15 µL of unfrozen plasma was mixed with 45 µL of ACN [51]. The mixture was vortexed (Vortex Genie 2, Scientific Instrument, USA) in a 200 µL Eppendorf tube for 3 min and then centrifuged under an acceleration force of 4000× g for 60 s (MiniSpin Plus personal microcentrifuge, Eppendorf, Hamburg, Germany), which is sufficient for complete precipitation of the plasmatic proteins.…”

Capillary electrophoresis for the investigation of two novel aminoalkanol derivatives of 1,7‐diethyl‐8,9‐diphenyl‐4‐azatricyclo[5.2.1.02,6] dec‐8‐ene‐3,5,10‐trione as potential anticancer drugs in water solution and serum

“…The advantages of CE include its simplicity, high efficiency, versatility, speed, high‐resolution power, small sample volume required, and low operating costs, as well as ability to analyze a diverse spectrum of analytes ranging from small organic ions to macromolecular protein complexes or DNA . CE is an analytical technique with an increasing role in biological, pharmacological, drug discovery, and clinical research . It seems to be the most commonly used technique that provides very good results in analyses of various substances, including active pharmaceutical ingredients .…”

A simple liquid chromatography coupled with tandem mass spectrometry approach for the simultaneous quantification of thirteen compounds in rats following oral administration of raw and processedFructus Xanthii: Application in a comparative pharmacokinetic study

“…Moreover, most research has only focused on the determination of phenolic acids alone, and no research about the simultaneous analysis of phenolic acids and diterpenoid glycosides in XF in vivo has been reported up to now. Preclinical pharmacokinetics has a very important influence on the development and investigation of potential candidates to provide better advice for further drug design . Pharmacokinetic studies can supply both toxicological and clinical information and facilitate the direct optimization of drug candidates; as a result, they play necessary parts in drug discovery and development .…”