Pharmaceutical Analysis Application Of Choromatographic Technology

1. PrefaceThe preface sets out to describe the history, the role and the trend of pharmaceutical analysis. It simply introduces the principle, the character, and numerous types of detectors of HPLC and CE technologies. It emphasize the quality control of drug substance by monitoring impurities, based on origin and types of impurities. HPLC has greatly evolved to offer numerous methods and analytical capabilities in pharmaceutical analysis, and the present state-of-art of HPLC for determination of impurities of analgesic, antibiotic, anti-viral, anti-hypertensive, anti-depressant, gastro-intestinal and anti-neoplastic agents has been discussed. Furthermore, this overview adds considerably to the literature describing the utility of CE as an analytical technique for drug substance quality control and drug in body fluid. This review covers around 185 analytical methods including all types of chromatographic and hyphenated techniques reported. 2. Studies of the Rate Constant of Levodopa Methyl Ester Hydrolysis byHPLCLevodopa methyl ester hydrochloride (LDME) is a highly soluble pro-drug produced by esterification of the carboxylic function of levodopa (L-DOPA) , as adjunctive therapy to relieve motor fluctuations in patients with Parkinsons' s disease who do not respond to therapy with L-DOPA or a decarboxylase inhibitor. Prior to releasing LDME on the market, detailed kinetic studies on new molecules of interest must be undertaken to provide quantitative data on the dependence of the reaction rate constant on, inter alia: temperature, pH, metal ions concentration and ionic strength. This paper first investigated the hydrolysis kinetics of levodopa methyl ester in 0.05-1.5 M HC1 between 37 and 75℃. An isocratic HPLC assay was developed for simultaneous determination of levodopa methyl ester and levodopa in the hydrolysate of levodopa methylester. A series of hydrolysis rate constants were obtained and the effects of hydrogen ion concentration and temperature on the reaction were evaluated. It was found that pH was a key factor at low temperature, but that when the temperature was raised, temperature became in turn the most influent factor on the hydrolysis. From the measured pseudo-first order reaction rate constants, the activation energies for levodopa methyl ester hydrolysis in 0.5, 1.0 and 1. 5 M HCl were calculated to be 71.24,74.32 and 76.57 kJ mol^-1, respectively.3. HPLC Method for the Determination of Assay and Purity of Levodopa Methyl Ester in Bulk and in Formulations and its Enantiomers by ChiralChromatographyLevodopa methyl ester hydrochloride (LDME) is administered in an enantiomerically pure form, as the racemic mixture can be hydrolyzed easily to dopa by plasma esterases in clinical use, and DOPA contains half of D- dopa which is inactive , and also toxic properties .Therefore, it is important to develop a method for separation and determination of enantiomers of dopa methyl ester. Anyway LDME contains related substances such as levodopa (L-DOPA), 3-methoxytyrosine (MTS) and L-tyrosine (TS). A novel, sensitive, reliable and reproducible method has been developed for separation and quantification of levodopa methyl ester (LDME) and its impurities such as levodopa (L-DOPA), 3-methoxytyrosine (MTS) and L-tyrosine (TS) in bulk drug and pharmaceutical dosage form, firstly using high-performance reversed-phase liquid chromatography with electrochemical detection (HPLC-ECD). The correlation coefficients of linear regression for LDME, L-DOPA, MTS and TS were more than 0. 999. The detection limits for L-DOPA, MTS and TS were 3. 15, 2.04 and 2.88 ng mL^-1, respectively. The precision was checked in terms of F-test variance ratio using potentiometric titration as reference. The ratio of variances of the two methods is close to unity, conforming their good precision. The enantiomeric separation of dopa methyl ester by chiral chromatography method has been described also. This method is capable of separating the two enantiomers with a selection of 1. 4 and a resolution of 8. 4. Both methods are found to be stabil...