Development and Validation of Chiral Separation of Some Enantiomeric Drugs by HPLC and LC-MS

Gowramma, B (2012) Development and Validation of Chiral Separation of Some Enantiomeric Drugs by HPLC and LC-MS. Doctoral thesis, The Tamilnadu Dr. M.G.R. Medical University, Chennai.


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This thesis deals with the studies carried out by the writer in the laboratory for the past four years on the development and validation of chiral separation of some enantiomeric drugs by HPLC and LC-MS methods. Thesis begins with a brief introduction of the reasons for analysing enantiomeric drugs and introduction to the analytical methods used like HPLC and LC-MS. The methods used for the quantitative analysis of enantiomers and the introduction to the chiral separation are given. Thesis deals with the aim and objective of the present work, the reasons for analysing the enantiomers and need for newer analytical methods for the estimation of enantiomers in pharmaceutical formulation are briefly discussed. Thesis deals with the reviews of literature on the analytical methods available for the estimation of the drug candidates in pharmaceutical formulations are explained. Thesis deals with the materials and instruments used in the experimental procedures adopted. It describes in detail the procedure adopted for the optimisation of the chromatographic conditions for the chiral separation of drugs by HPLC and LC-MS methods and for the estimation of enantiomers in the selected drug candidates are presented and discussed. Forced degradation studies on the selected racemic drugs using acid, alkaline, neutral, oxidative and photolytic degradations and quantification of enantiomers by HPLC in different stress conditions are presented and discussed. The results obtained are presented and discussed. HPLC and LC-MS chromatograms of the standard and sample solutions, calibration curves for the selected analytes are also presented. The results of the experiments carried out to check the accuracy, reproducibility of the methods carried out are presented and discussed in detail. System suitability studies and forced degradation studies carried out for various methods developed are also presented and discussed. The following are some of the salient features and conclusions made for the present study. • Four racemic drugs namely Rosiglitazone, Pioglitazone, Zaltoprofen and Valganciclovir Hydrochloride for which there were no HPLC and LC-MS methods reported for the estimation of enantiomers in pharmaceutical formulations and their stability in different stress conditions were selected for the present study after thorough literature survey. • The chromatographic conditions like detection wavelength/mass range, nature and composition of mobile phase, nature of stationary phase, peak modifiers, flow rate etc were optimised for the best possible separation and quantification of the analytes. Forced degradation studies on the selected racemic drugs using acid, alkaline, neutral, oxidative and photolytic degradations were performed. • The developed HPLC and LC-MS methods were validated for their transferability to other laboratories, in terms of specificity, selectivity, accuracy, precision, linearity and range, detection and quantification limits, ruggedness, robustness and system suitability. The validation studies carried out revealed that the developed methods satisfy the ideal characteristics of the analytical methods. • The direct and indirect chiral HPLC and LC-MS methods developed in the present study for the estimation were found to be simple, rapid, accurate, precise, specific, linear and rugged. They are thus suitable for the estimation of enantiomers in raw materials and formulations. The newly developed analytical methods can be used in the following fields: • Research institutions, • Academic institutes, • Quality control department in industries, • Approved testing laboratories, • Biopharmaceutics and bioequivalence studies and • Clinical and pharmacokinetic studies after suitable modification.

Item Type: Thesis (Doctoral)
Uncontrolled Keywords: Development, validation ; chiral separation ; enantiomeric drugs, High Performance Liquid Chromatography (HPLC), Liquid chromatography–mass spectrometry (LC-MS).
Subjects: PHARMACY > Pharmaceutical Chemistry
Depositing User: Subramani R
Date Deposited: 19 Aug 2017 03:46
Last Modified: 27 Oct 2022 14:13

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