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 × 50mm, 1.7um) and a mobile phase that consisted of 5 mM 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 0.4ml/min with fluorescence detection using an excitation wavelength of 230nm and emission detection wavelength of 315nm. 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 - 50.02%) and (54.65 - 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.