BIO-ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR THE SIMULTANEOUS ESTIMATION OF DECITABINE AND CEDAZURIDINE IN HUMAN PLASMA USING LC-MS/MS

SAI PRUDHVI N.; VENKATESWARLU B. S.; KUMUDHAVALLI M. V.; MURUGANANTHAM V.

doi:10.22159/ijap.2021v13i5.41744

Authors

SAI PRUDHVI N. Vinayaka Missions College of Pharmacy, Salem, India, Department of Pharmaceutical Analysis, M. A. M. College of Pharmacy, Guntur, India
VENKATESWARLU B. S. Department of Pharmaceutical Analysis, M. A. M. College of Pharmacy, Guntur, India
KUMUDHAVALLI M. V. Department of Pharmaceutical Analysis, Vinayaka Missions College of Pharmacy, Salem, India
MURUGANANTHAM V. Department of Pharmaceutics, Vinayaka Missions College of Pharmacy, Salem, India

DOI:

https://doi.org/10.22159/ijap.2021v13i5.41744

Keywords:

Decitabine, Cedazuridine, LCMS analysis, Human plasma, Bio-analytical method

Abstract

Objective: The present work aimed to develop a novel, reliable and accurate Liquid Chromatography-Mass Spectrometry/Mass spectrometry (LC-MS/MS) method for the simultaneous quantification of Decitabine and Cedazuridine a combined medication used for the treatment of chronic myelomonocytic leukemia in human plasma.

Methods: Talazoparib drug is used as an internal standard in the study. Both the analytes and internal standard were isolated from 100 ml plasma samples by liquid-liquid extraction and then chromatographed on Zorbax SB-CN (4.6 mm×75 mm, 3.5 µm) column with a mobile phase consisting of 0.1 % ammonium formate and methanol in the ratio of 65:45 (v/v) pumped at 0.5 ml/min. The method had a chromatographic total run time of 5 min.

Results: The developed method gave a symmetric peak at a retention time of 1.7 min for Decitabine, 2.2 min for Cedazuridine, 3.5 min for Talazoparib and satisfied all the peak properties as per USP guidelines. The mass spectral characterization of separated analytes in the LC method was performed using a mass detector operated at Multiple Reaction Monitoring mode with precursor-to-product ion transitions at m/z of 229 to m/z of 114 as MH⁺ion for Decitabine, m/z of 269 to m/z of 118 as MH⁺ion for Cedazuridine. A very sensitive limit of detection of 0.3 ng/ml was observed and showed a calibration curve linear over the concentration range of LLOQ (lower limit of quantification) to 500 ng/ml. The other validation parameters were found to have acceptable accuracy, precision, linearity, and selectivity. The mean extraction concentration was acceptable and very high for both the analytes in HQC (high-quality control concentration), MQC (medium quality control concentration) and LLOQ levels. The peak area response ratio of Decitabine and Cedazuridine with the internal standard in freeze-thaw, short term and long term stability studies was found to be acceptable confirms that the method is stable.

Conclusion: It can be concluded that the proposed method is specific, accurate, and precise and could be used for the simultaneous estimation of Decitabine and Cedazuridine in human plasma.

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