1055 Available online at www.joac.info ISSN: 2278-1862 Journal of Applicable Chemistry 2014, 3 (3):1055-1058 (International Peer Reviewed Journal) Investigation of Z-E Isomerism in Sunitinib Anticancer drug Sharwan K. Dewan 1* , Sangeeta Sangwan 2 , R Thapar 2 and Mohan Prasad 2 1. Department of Chemistry, M. D. University, Rohtak - 124001, Haryana, INDIA 2. Chemical Research Department, Ranbaxy Laboratories Limited, Research & Development Centre, Sarhaul, Sector-18, Gurgaon - 122015, Haryana, INDIA Email: sharwankumardewan@yahoo.com Accepted on 8 th April 2014 _____________________________________________________________________________ ABSTRACT Z-E isomerization in sunitinib, an important anticancer drug, has been investigated. The influence of light, heat and solvent was studied and the isomerizations were monitored by HPLC. As expected, the extent of Z-E isomerization (conversion of the Z-isomer into the undesired E-isomer) is found to depend on these parameters. In addition, both reversible and irreversible isomerizations were observed when the solutions were kept in dark following the exposures to light. These observations have implications in the analysis of sunitinib samples using HPLC methods. Keywords: Sunitinib, Z-E isomerism, photo-isomerization and thermal-isomerization. ______________________________________________________________________________ INTRODUCTION Sunitinib is a vascular endothelial growth factor receptor inhibitor which has demonstrated a high activity in renal cell carcinoma. This is currently used in the treatment of patients with metastatic disease[1-2]. It is sold as malate salt by Pfizer under the brand name Sutent. Sunitinib is a yellow to orange powder with a solubility of 25mg mL -1 in acidic solutions (pH 1.2 - 6.8) [3]. It has an exocyclic double bond at the 3- position of the oxindole ring and therefore can exhibit Z-E isomerism. It has been shown that SU5416, closely related to sunitinib, undergoes photo induced transformation into the less stable E isomer in solution[4]. Light[5-6] and heat[7-8] induced isomerization of compounds containing C=C and N=N double bonds is well documented in the literature[5-8]. Studies in the analytical solution, non-aqueous formulation and blood plasma have revealed that the extent of conversion of the Z-isomer into the E- isomer depends on the concentration, polarity and viscosity of the media. In addition, these authors have also shown that the Z-E isomerization of SU5416 is reversible. When the pre-exposed solutions are kept in dark, the E-isomer content was found to be less than 0.3%. In the present study, we report the synthesis of sunitinib and results of Z-E isomerization in sunitinib in various organic solvents. MATERIALS AND METHODS All the API intermediates and reagents were provided by Ranbaxy Laboratories Ltd., India. Waters HPLC 2695 alliance separation module (customized with syringe and loop volume of 2.5 mL) with PDA 2998 detector was used for. HPLC grade solvents were used as obtained from Rankem and Qualigens. Kromasil