Simultaneous determination of L-tetrahydropalmatine and cocaine in human plasma by simple UPLC-FLD method: application in clinical studies.

Abstract

Currently, there are no FDA approved medications for treatment of cocaine addiction underscoring the dire need to develop such a product. There is an accumulating body of evidence that l-tetrahydropalmatine (l-THP), a non-selective dopamine antagonist, can be used for the treatment of cocaine addiction. Indeed, the FDA recently approved its usage in a Phase I study in cocaine abusers and it was indispensable to develop a simple and sensitive method for the simultaneous determination of l-THP and cocaine in human plasma. We developed a UPLC-FLD method for quantitation of these molecules using an ACQUITY BEH C18 column (2.1 mm × 50mm, 1.7 μm) and a mobile phase that consisted of 10mM ammonium phosphate (pH=4.75), methanol, and acetonitrile (v:v:v, 78:16:6). Venlafaxine was used as the internal standard while hexane was used for the liquid-liquid extraction. The flow rate was 0.4 mL/min with fluorescence detection using an excitation wavelength of 230 nm and emission detection wavelength of 315 nm. This method was selective, linear and sensitive with a lower limit of quantification of 2.5 ng/mL for both cocaine and l-THP. The intra-day precision of cocaine and l-THP was <9.50% while the accuracy was <4.29%. The inter-day precision of cocaine and l-THP was <9.14%, and the accuracy was <12.49%. The recovery for cocaine and l-THP ranged from 43.95 to 50.02% and 54.65 to 58.31%, respectively. In comparison to forty reported cocaine quantitation methods this method is simple, sensitive and cost-effective and can be used for simultaneous quantitation of l-THP and cocaine. This method meets the FDA guidelines and can be used in current and future clinical studies.

• Authors: Mingming Yu, Hazem E Hassan, Ahmed Ibrahim, Kenneth S Bauer, Deanna L Kelly, Jia Bei Wang
• Journal: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences (J Chromatogr B Analyt Technol Biomed Life Sci) Vol. 965 Pg. 39-44 (Aug 15 2014) ISSN: 1873-376X [Electronic] Netherlands
• PMID: 24996068 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Berberine Alkaloids
• tetrahydropalmatine
• Cocaine

Topics

• Berberine Alkaloids (blood, chemistry, pharmacokinetics)
• Chromatography, High Pressure Liquid (methods)
• Cocaine (blood, chemistry, pharmacokinetics)
• Drug Stability
• Humans
• Linear Models
• Liquid-Liquid Extraction
• Reproducibility of Results
• Sensitivity and Specificity
• Spectrometry, Fluorescence