DETERMINATION OF HYDROLYSIS PARAMETERS OF YOHIMBINE HCl AT NEUTRAL AND SLIGHTLY ACIDIC MEDIUM
Keywords:
Yohimbine HCl, Yohimbinic acid, Stability, pH, Hydrolysis, Kinetic, Activation, EnergyAbstract
Objectives: In the process of investigating various new drug delivery systems of yohimbine HCl (Yoh), it was necessary to study some of the physical chemical properties of the drug including its stability at neutral, acidic and slightly acidic conditions.
Methods: A validated HPLC method was developed and employed for analysis of Yoh containing solutions. The mobile phase composed of 60% menthol: 40% NaOAc (%v/v), and Gemi C18 column, 5 µm particle size was used as a stationary phase. The degradation product was found to be yohimbinic acid (YA). The retention times for Yoh and YA were 5 and 3 minutes, respectively. This study investigated the kinetics of hydrolysis of Yoh at pH 6.0 and 7.0 at temperatures from 50 °C to 80 °C.
Results: The reaction followed first order kinetics and the activation energy ∆E of the reaction at pH 6 and pH 7 was found to be 16.2 and 16.8 Kcal. mole-1, respectively. While the values of A were found to be 41.8 and 44.1 Kcal. mole-1 at pH 6 and 7, respectively. The pseudo first order rate constants (K) at pH 6 and 7 were calculated as 2.76 х 10 -3 h-1 and 3.42 х 10 -3 h-1, respectively.
Conclusion: Such results indicate high stability of the drug at these pH values. At highly acidic medium the reaction was found to be extremely slow indicating the absence of acid catalysis on the hydrolysis of Yoh. Thus, the yohimbine ester group resists hydrolysis in highly acidic conditions.
Â
Downloads
References
Ernst E, Pi’itler M. Yohimbine for erectile dysfunction: a systematic review and meta-analysis of randomized clinical trials. J Urol 1998;159:433-6.
Cimolai N, Cimolai T. Yohimbine use for physical enhancement and its potential toxicity. J Diet Suppl 2011;8(4):346-54.
Aronson J. Meyler's side effect of drugs. 15th ed. Oxford (UK): Elsevier; 2006.
Bhattacharya S, Clow A, Przuborowska A, Halket J, Glover V, Sandler M. Effect of aromatic amino acids, pentylenetetrazole and yohimbine on isatin and tribulin activity in rat brain. Neurosci-Lett 1991;28(132, Suppl 1):44-6.
Brodd O, Anlauf M, Arroyo J. Hypersensitivity of adrenergic receptors and blood pressure response to oral yohimbine in orthostatic hypotension. New Engl J Med 1983;17:1033-4.
Bourin M, Malinge M, Colombel M, Larousse C. Influence of alpha stimulants and beta blockers on yohimbine toxicity. Prog Neuropsychopharmacol Biol Psychiatry 1988;12:569-74.
Schwager A, Haack A, Taha S. Impaired flexibility in decision making in rats after administration of the pharmacological stressor yohimbine. Psychopharmacol (Berl) 2014;231 (20):3941-52.
Corazza O, Martinotti G, Santacroce R, Chillemi E, Di Giannantonio M, Schifano F, et al. Sexual enhancement products for sale online: raising awareness of the psychoactive effects of yohimbine, maca, horny goat weed, and Ginkgo biloba. Biomed Res Int 2014;2014:1-13.
William S, Manuel W, Michael W. Yohimbine: a clinical review. Pharmacol Ther 2001;91(3):215–43.
Linden C, Vellman W, Rumack B. Yohimbine a new street drug. Am Emerg Med 1985;14:1002-4.
Owen J, Nakatsu S, Fenemore J, Condra M, Surridge D, Morales A. The pharmacokinetics of yohimbine in man. Eur J Clin Pharmacol 1987;32(6):577-82.
Guthrie S, Hariharan M, Grunhaus L. Yohimbine bioavailability in humans. Eur J Clin Pharmacol 1990;39(4):409-11.
Papl M, Fahnrich J. Chromatogrpahic analysis of alkaloids. Marcel Dekker, New York; 1990.
Farouk M, Abd El-Aziz L, El-Gindy A, Shokry E. Validated methods for determination of yohimbine hydrochloride in the presence of its degradation products. B-FOPCU 2011;49(2):67–79.
Awad R. kinetics and mechanism of decomposition of yohimbine in alkaline medium. Alex J Pharm Sci 1991;5(1):74-7.
Carey F, Giuliano R. Organic chemistry. 8th ed. New York (USA): McGraw Hill; 2010.