title: 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.affiliation: Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
authors.forename: Hazem E
authors.initials: HE
authors.lastname: Hassan
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ibrahim
authors.affiliation: Department of Pharmacy Practice and Science, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Bauer
authors.affiliation: Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD 21228, USA.
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Kelly
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA. Electronic address: jwang@rx.umaryland.edu.
authors.forename: Jia Bei
authors.initials: JB
authors.lastname: Wang
mesh_terms: D001600:Berberine Alkaloids / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003042:Cocaine / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D006801:Humans; D016014:Linear Models; D059625:Liquid-Liquid Extraction; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence
chemical_list: D001600:Berberine Alkaloids; C014215:tetrahydropalmatine; D003042:Cocaine
keywords: Analysis; Cocaine; Fluorescence; Human plasma; UPLC; l-THP