Studies of the Rate Constant of l-DOPA Oxidation and Decarboxylation by HPLC

被引：0
作者：
Yong Zhi Zhou
Raid G. Alany
Victor Chuang
Jingyuan Wen
机构：
[1] The University of Auckland,Drug Delivery Research Unit, School of Pharmacy, Faculty of Medical and Health Sciences
[2] Kingston University London,School of Pharmacy and Chemistry
[3] Kingston Upon Thames,School of Pharmacy, Faculty of Health Sciences, Curtin Health Innovation Research Institute
[4] Curtin University,undefined
来源：
Chromatographia | 2012年 / 75卷
关键词：
Column liquid chromatography; -DOPA; Oxidation; Decarboxylation; Rate constant;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
The objective of current investigation was to study the degradation behavior of l-DOPA under different conditions by high performance liquid chromatography (HPLC), and to develop and validate a stability-indicating HPLC method. The developed RP-HPLC method was validated with respect to linearity, accuracy, precision and specificity. Oxidation was found to occur in alkaline and to some extent in thermal conditions, while the drug was stable when incubated at acidic conditions and under photolytic stress. The oxidation of l-DOPA was observed to follow first-order kinetics. The degradation rate constants and half-life were calculated. The cytotoxicity and enzymatic degradation of l-DOPA was examined using the human intestinal epithelial Caco-2 cells. The drug was rapidly decarboxylated by aromatic amino acid decarboxylase to dopamine. The conversion of l-DOPA to dopamine was dose- and time-dependent.
引用
收藏
页码：597 / 606
页数：9
相关论文
共 150 条
[1]  
Moos T(2004)Absence of prostate apoptosis response-4 protein in substantia nigra of Parkinson’s disease autopsies Acta Neurophathol 107 23-26
[2]  
Jensen PH(1988)Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson’s disease N Engl J Med 318 876-880
[3]  
Kish SJ(2000)Manganese increases Br J Pharmacol 130 937-945
[4]  
Shannak K(1993)-DOPA auto-oxidation in the striatum of the freely moving rat: potential implications to Int J Pharm 99 135-143
[5]  
Hornykiewicz O(1989)-DOPA long-term therapy of Parkinson’s disease Br J Clin Pharmacol 28 61-69
[6]  
Serra PA(2000)Macromolecular prodrugs. II. Esters of Pharm Res 17 978-984
[7]  
Esposito G(2001)-dopa and [alpha]-methyldopa Food Chem 72 389-394
[8]  
Enrico P(1985)The effect of age on the pharmacokinetics of levodopa administered alone and in the presence of carbidopa Biochem Pharmacol 34 1801-1807
[9]  
Mura MA(1995)Enhancement of the systemic and CNS specific delivery of J Neurochem 64 825-832
[10]  
Migheli R(2001)-Dopa by the nasal administration of its water soluble prodrugs J Pharm Sci 90 253-269
12345678910