SEPARATION AND DETERMINATION OF THE R-ISOMER OF KETOPROFEN IN A BULK DRUG SUBSTANCE BY NORMAL PHASE LIQUID CHROMATOGRAPHY
Objective: The objective is defined to develop and validate simple, rapid, precise, and accurate for separation and determination of R-isomer impurity of ketoprofen bulk drug material by the normal phase high-performance liquid chromatographic method as per the International Conference of Harmonization Guideline (ICH) guidelines.
Methods: The R-isomer and S-isomer were baseline resolved on a Chiralcel OJ-H, 150 mm Ã— 4.6 mm, and 5 Âµm stationary phase column. Mobile phase system containing n-hexane:isopropyl alcohol:glacial acetic acid (50:50:0.1 v/v.). The detector wavelength has been selected 254 nm and column oven temperature 25Â°C. The chromatographic resolutions between R-isomer and S-isomer were more than two. The developed method was extensively validated according to ICH guidelines.
Results: Ketoprofen linearity was found for R-isomer over the concentration range of 600-6000 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 ketoprofen R-isomer were found to be 200 and600 ng/ml. The percentage recovery of R-isomer has been ranged from 97.5 to 102.0 in bulk drug material samples of ketoprofen. The proposed method was found to be suitable and accurate for the quantitative determination of R-isomer of ketoprofen in bulk drug sample.
Conclusion: A simple, rapid, precise, and accurate normal phase liquid chromatography method has been developed and validated to determineR-isomer impurity of ketoprofen in bulk drugs material as per ICH.
Keywords: Ketoprofen, High-performance liquid chromatography, Known impurity, Normal phase, Chiralcel OJ-H, Validation.
2. Guo Z, Wang H, Zhang Y. Chiral separation of ketoprofen on an achiral C8 column by HPLC using norvancomycin as chiral mobile phase additives. J Pharm Biomed Anal 2006;41(1):310-4.
3. Blanco M, Coello J, Iturriaga H, Maspoch S, Perez-Maseda C. Chiral and non-chiral determination of ketoprofen in pharmaceuticals by capillary zone electrophoresis. J Chromatogr A 1998;799(1-2):301-7.
4. International Conference on Harmonization Guidance for Industry in: Q2A Text on Validation of Analytical Methods. Switzerland: IFPMIA: 1994. p. 4.
5. International Conference on Harmonization Guidance for Industry in: Q2B Text on Validation of Analytical Methods. Switzerland, IFPMIA: 1996. p. 1-8.
6. Jadhav HP, Pathare DB. Separation and determination of the S-isomer of (10 camphorsulfonyl) oxaziridine in a bulk drugs substance by normal phase liquid chromatography. Int J Pharm Pharm Sci 2015;7(7):66-9.
7. Mali AD. Simultaneous determination of carvedilol and hydrochlorothiazide in pharmaceutical dosage form by first order derivative UV spectrophotometry. Int J Pharm Pharm Sci 2015;7(9):371-4.
8. Jadhav HP. Determination of R-isomer impurity of pantoprazole sodium in a bulk drug substance by normal phase chiral liquid chromatography method. Int J Pharm Pharm Sci 2015;7(8):45-8.
9. Raul SK, Aravelli AB. RP-HPLC method development and validation for the simultaneous estimation of atorvatanin and ezetimibe in pharmaceutical dosage form. Asian J Pharm Clin Res 2015;8(2):178-81.
10. USFDA. Reviewers Guidance: Validation of Chromatographic Methods. Washington DC: Food and Drug, Centre for Drug Evaluation and Research; 1994. p. 1-29.
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