TRACE LEVEL DETERMINATION AND QUANTIFICATION OF POTENTIAL GENOTOXIC IMPURITIES IN DASATINIB DRUG SUBSTANCE BY UHPLC/INFINITY LC
DOI:
https://doi.org/10.22159/ijpps.2016v8i10.14020Keywords:
Genotoxic impurities, Dasatinib, UPLC, UHPLC, QbD, Infinity-LC, ValidationAbstract
Objective: A simple, cost-effective and mass compatible ultra-high fast performance liquid chromatographic (Agilent-Infinity LC 1290) method has been developed and validated for the determination of potentially genotoxic impurities in dasatinib active pharmaceutical ingredients.
Methods: This method comprises the determination of three possible genotoxic impurities in dasatinib. The mobile phase is trifluoroacetic acid, acetonitrile and water with linear gradient elution curve number 6. The column used for the development and validation is zorbax RRHD eclipse plus C18 with the length of 50 mm, the internal diameter of 2.1 mm and particle size of 1.8 microns.
Results: The limit of detection of the potential genotoxic impurities are less than 0.1 µg/ml with respect to dasatinib test concentration of 1000 µg/ml. The limit of quantification of the potential genotoxic impurities is less than 0.3 µg/ml with respect to dasatinib test concentration of 1000 µg/ml.
Conclusion: This method has been validated as per ICH guidelines Q2 (R1). These three potential mutagenic impurities are not degradant impurities of dasatinib and its only process related impurities. The method development has been approached using the QbD principle.
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NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. US department of health and human Services, public health service, centers for disease control and prevention, national Institute for occupational; 2004. p. 1-29.
Safety and health, DHHS (NIOSH) publication; 2004. p. 165.
Mohammed G Kassem, Essam Ezzeldin, Hesham M Korashy, Gamal AE Mostafa. A high-performance liquid chromatographic method for the determination of dasatinib in rabbit plasma using fluorescence detection and its application to a pharmacokinetic study. J Chromatogr B 2013;939:73-9.
Michael TF, Shruti A, Dara H, Michael L, Steve U, Linda K, et al. A validated LC-MS/MS assay for the simultaneous determination of the anti-leukemic agent dasatinib and two pharmacologically active metabolites in human plasma: application to a clinical pharmacokinetic study. J Pharm Biomed Anal 2012;58:130-5.
Silvia DF, Antonio DA, Francesca DM, Elisa P, Lorena B, Marco S, et al. New HPLC-MS method for the simultaneous quantification of the antileukemia drugs imatinib, dasatinib, and nilotinib in human plasma. J Chromatogr B 2009;877:1721-6.
Rao KNV, Srivani P, Raja MA, Banji D, Kumar DS. Analytical method development and validation of dasatinib in its pharmaceutical dosage form by UPLC with forced degradation studies. Int J Pharm Res Scholars 2013;2:221-7.
Ramachandra B, Suguna B, Sivarami Reddy P, Naidu NVS. Development of a UV-visible spectrophotometric method for determination of dasatinib in pharmaceutical formulation and biological samples. Int J Pharm Sci Res 2015;6:293-303.
Ramachandra B, Naidu NVS. Validation of RP-HPLC method for estimation of dasatinib in bulk and its pharmaceutical dosage forms. Int J Pharm Biol Sci 2014;4:61-8.
Sreedevi A, Lakshmana Rao A. Development and validation of novel HPLC method for the estimation of dasatinib in bulk and pharmaceutical dosage forms. Int J Res Pharm Chem 2013;3:724-9.
Alagar Raja M, Namratha CH, David Banji, Rao KNV, Selvakumar D. RP-HPLC method for estimation of dasatinib in active pharmaceutical ingredient and pharmaceutical dosage form as per ICH guidelines. Asian J Pharm Anal Med Chem 2015;3:109-16.
Vivekananda Reddy D, Sreelatha P, Rama Devi B. A novel stability indicating assay method development and validation of dasatinib tablets formulations. Chem Sci Rev Lett 2014;3:747-58.
Antonio D’Avolio, Marco Simiele, Silvia De Francia, Alessandra Ariaudo, Lorena Baietto, Jessica Cusato, et al. HPLC–MS method for the simultaneous quantification of the antileukemia drugs imatinib, dasatinib and nilotinib in the human peripheral blood mononuclear cell (PBMC). J Pharm Biomed Anal 2012;59:109-16.
Thulase Nadh Reddy Dodda, Regalla Narasimha reddy, Meghana Reddy Regalla. Method development and validation of stability indicating RP-HPLC method for the estimation of dasatinib in tablet dosage form. Indo Am J Pharm Res 2013;3:1331-45.
Jiazhi Wang, Yunfang Zhou, Cheng Wang, Jianmiao Chen. Simultaneous determination of lapatinib, cabozantinib, imatinib, dasatinib, sorafenib, crizotinib, erlotinib and saha in rat plasma by UPLC-MS/MS. Latt Am J Pharm 2015;34:1576-84.
Yunfang Zhou, Shuanghu Wang, Ting Ding, Mingdong Wu, Peiwu Geng, Qingwei Zhang, et al. Pharmacokinetic interaction study of combining imatinib with dasatinib in rats by UPLC-MS/MS. Drug Dev Ind Pharm 2015;41:1948-53.
Hari Babu B, Bala Murali Krishna K, Rama Krishnaveni P. Development and validation of HPLC method for the estimation of lapatinib in bulk drugs and pharmaceutical formulations. Int J Res Rev Pharm Appl Sci 2011;1:207-14.
Mhaske DV, Dhaneshwar SR. Stability indicating HPTLC and LC determination of dasatinib in pharmaceutical dosage form. Chromatographia 2007;66:1-2.
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf. [Last accessed on 10 Jun 2016].
http://www.oecd.org/chemicalsafety/testing/oecdquantitativestructure-activityrelationshipsprojectqsars.htm. [Last accessed on 10 Jun 2016].
Kunal Roy, Supratik Kar, Rudra Narayan Das. Understanding the basics of QSAR for applications in pharmaceutical sciences and risk assessment, Academic press, Elsevier, New York, 2015.
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1B/Step4/Q1B_Guideline.pdf. [Last accessed on 10 Jun 2016].
Uma G, Najila Banu A, Sathica Taj A, Josephine Benedit Bai U. Phytochemical screening and antibacterial activity of scoparia dulcis extracts. Asian J Pharm Clin Res 2014;7:130-3.
Anila KN, Emmanuel J. Clinical pharmacist, governed anticoagulation service in stroke unit of a tertiary care teaching hospital. Asian J Pharm Clin Res 2013;6:149-52.
Sivamani S, Benin Joseph, Bibhas Kar. Zebrafish: an emerging model system for drug discovery. Asian J Pharm Clin Res 2016;9:11-4.
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Multidisciplinary/M7/M7_Step_4.pdf. [Last accessed on 10 Jun 2016].
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021986s000_Sprycel__ClinPharmR.pdf. [Last accessed on 10 Jun 2016].
http://www.drugbank.ca/drugs/DB01254. [Last accessed on 10 Jun 2016].
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