ENANTIOMERIC SEPARATION OF ETODOLAC IN A BULK DRUG SUBSTANCE BY REVERSE-PHASE CHIRAL LIQUID CHROMATOGRAPHY METHOD
Keywords:
Etodolac, Reverse phase, Chiral HPLC, Validation, Solution and mobile phase stabilityAbstract
Objective: To develop novel, simple and rapid enantiomeric separation of Etodolac by reverse-phase high-performance liquid chromatographic method as per ICH guidelines.
Methods: The R-isomer and S-isomer were baseline resolved on a CHIRAL-AGP, (100 x 4.0 mm i. d, 5 mm) column using a mobile phase system containing 0.1 M sodium dihydrogen phosphate dihydrate pH 4.0 buffer: Isopropanol (85:15 v/v.) at detector wavelength 225 nm and column temperature 25 °C. The chromatographic resolutions between R-isomer and S-isomer were found three. The developed method was extensively validated according to ICH guidelines.
Results: Good linearity was observed for R-isomer over the concentration range of 300–3000 ng/ml, with the linear regression (Correlation coefficient R = 0.999) and proved to be robust. The limit of detection and limit of quantification of R-isomer was found to be 300 and 900 ng/ml, respectively for 10 ml injection volume. The percentage recovery of R-isomer was ranged from 98.0 to 102.0 in bulk drug samples of Etodolac. Etodolac sample solution and mobile phase were found to be stable for at least 48 hours. The proposed method was found to be suitable and accurate for the quantitative determination of R-isomer in bulk drugs.
Conclusion: A novel, simple and rapid enantiomeric separation of Etodolac by reverse-phase high-performance liquid chromatographic method was developed and validated as per ICH guidelines. The developed method can be used for the quantitative determination R-isomer in bulk drug materials in pharmaceutical industry.
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References
Chang CG, Yi HT, Hai HH, Lu SY, Hui DJ, Su Z. Analysis of chiral non-steroidal anti-inflammatory drugs flurbiprofen, ketoprofen and etodolac binding with HSA. J Pharm Anal 2011;1(3):184-90.
Caccamese S. Direct high-performance liquid chromatography (HPLC) separation of etodolac enantiomers using chiral stationary phases. Chirality 1993;5(3):164-7.
Balan P, Carolin Nimila I, Lakshmi Prasanna M, Vanaja Rani M, Rajasekar S. RP-HPLC method development and validation of etodalac and paracetamol in combined dosage form. Asian J Res Chem 2011;4(7):1073-6.
Phan TD, Tran QT, Kyeong HK. Preparative resolution of etodolac enantiomers by preferential crystallization method. Arch Pharmacal Res 2009;32(10):1425-31.
Nishi H, Terabe S. Optical resolution of drug by capillary electrophoretic techniques. J Chromatogr A 1995;69:245-76.
Beckerscharfenkamp U, Blaschake GJ. Evaluation of the steroselective metabolism of the chiral analgesic drug etodolac. J Chromatogr B 1993;621:199-207.
Chou S, Tseng C, Chang L. Exploration of an efficient method for optical resolution of etodolac. J Chin Chem Soc 2001;48:229-34.
Xuejun Z, Zou L, Baochun S, Juanjuan C, Xiuzhu X. Enantioseparation of Anti-Inflammatory Agent on chiral stationary phase. J Anal Sci Methods Instrum 2012;2:18-22.
Menon S, Kadam N, Gursale A, Gokarn V, Palekar A. A Randomized, Crossover study to determine bioequivalence of S-Etodolac ER tablets versus etodolac ER tablets in healthy indian subjects. J Appl Res 2009;9(3):57-64.
ICH draft Guidelines on validation of analytical procedures. Definitions and Terminology. Federal Register IFPMA Switzerland 1995;60:11260-2.