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18. Analysis of carbenoxolone by ultra-high-performance liquid chromatography tandem mass spectrometry in mouse brain and blood after systemic administration.

Author

Poklis JL, Gonek MM, Wolf CE, Akbarali HI, and Dewey WL

Subjects
Animals, Carbenoxolone administration & dosage, Carbenoxolone chemistry, Carbenoxolone pharmacokinetics, Drug Stability, Injections, Intraperitoneal, Limit of Detection, Linear Models, Male, Mice, Reproducibility of Results, Brain Chemistry physiology, Carbenoxolone analysis, Chromatography, High Pressure Liquid methods, Tandem Mass Spectrometry methods
Abstract

Carbenoxolone is a derivative of glycyrrhetinic acid found in the root of Glycyrrhiza glabra, colloquially known as licorice. It has been used as a treatment for peptic and oral ulcers. In recent years, carbenoxolone has been utilized in basic research for its ability to block gap junctional communication. Better understanding the distribution of carbenoxolone after systemic administration can lead to a better understanding of its potential sites of action. Presented is an ultra high-performance liquid chromatography tandem mass spectrometer (UHPLC-MS/MS) method for the identification and quantification of carbenoxolone in mouse blood and brain tissue. Twenty mice were injected intraperitoneally with 25 mg/kg carbenoxolone and brain tissue and blood were collected for analysis. Blood concentrations (mean ± SD) at 15, 30, 60 and 120 min were determined to be (n = 5) 5394 ± 778, 2636 ± 836, 1564 ± 541 and 846 ± 252 ng/mL, respectively. Brain concentrations (mean ± SD) at 15, 30, 60 and 120 mins were determined to be (n = 5) 171 ± 62, 102 ± 35, 55 ± 10 and 27 ± 9 ng/g, respectively. The analysis of these specimens at the four different time points resulted in blood and brain half-lives in mice of ~43 and 41 min, respectively. The UHPLC-MS/MS method was determined to be sensitive and robust for quantification of carbenoxolone., (© 2018 John Wiley & Sons, Ltd.)

Published
2019
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19. Detection and quantification of tricyclic antidepressants and other psychoactive drugs in urine by HPLC/MS/MS for pain management compliance testing.

Author

Poklis JL, Wolf CE, Goldstein A, Wolfe ML, and Poklis A

Subjects
Antidepressive Agents, Tricyclic chemistry, Humans, Reproducibility of Results, Sensitivity and Specificity, Antidepressive Agents, Tricyclic urine, Chromatography, High Pressure Liquid methods, Pain drug therapy, Pain urine, Pain Management methods, Patient Compliance, Tandem Mass Spectrometry methods
Abstract

A sensitive, specific, and rapid high-pressure liquid chromatography/mass spectrometry/mass spectrometry method was developed for the quantitation of 11 tricyclic antidepressants and/or their metabolites; fluoxetine and norfluoxetine; cyclobenzaprine; and trazodone in urine. Samples were alkalinized with 0.2 N NaOH and extracted into 2 ml of hexane: ethyl acetate (1:1), evaporated to dryness, and reconstituted with 100 μl of 20 mM ammonium formate: methanol (20:80). The chromatographic separation was performed using an Allure Biphenyl 100 × 3.2 mm, 5-μ column with a mobile phase consisting of 20 mM ammonium formate: methanol (20:80 v/v) at a flow rate of 0.5 ml/min. The detection was accomplished by multiple-reaction monitoring via electrospray ionization source operating in the positive ionization mode. The calibration curve was linear over the investigated concentration range, 25-2,000 ng/ml, for each analyte using 1.0 ml of urine. The lower limit of quantitation for each analyte was 25 ng/ml. The intra- and inter-day precisions had coefficient of variation less than 15% and the accuracy was within the range from 88% to 109%. The method proved adequate for the tricyclic antidepressants analysis of urine for emergency clinical toxicology and pain management compliance testing., (© 2012 Wiley Periodicals, Inc.)

Published
2012
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