International Journal of Pharma Research & Review, Sept 2013; 2(9):10-15 Divyesh Patel et.al, IJPRR 2013; 2(9) 10 Research Article A Novel Potentiometric Titration Method for Quantitative Determination of Bromide Content in Doxorubicin Hydrochloride *Divyesh Patel, Samir Patel, Yogendra Parmar, Kamlesh Chauhan, Pooja Sannigrahi, A. S. Rawat, Anand Vardhan Analytical Department, Sterling Biotech Limited, Vadodara-391421, Gujarat, India. ________________________________________________________________________________________________________________________________________________________ ABSTRACT A simple precise, rapid accurate and sensitive Potentiometric titration method was developed for quantitative determination of Bromide content in Doxorubicin Hydrochloride. The titration was carried out by using standardized 0.1 N Silver Nitrate solutions (AgNO3). To confirm the presence of bromide content spiking study was carried out by spiking 0.1% NaBr into the test preparations which shows the 0.1 % increase in the % Cl of the actual % Cl. The end point was determined by using Mettler T 50 Auto titrator with DM 141 SC electrode. The proposed method was found to be precise with % RSD <1 (n = 6). The method showed strict linearity (r 2 > 0.999) between 0.5% to 4.0%. The percentage recovery of Bromide in the optimized method was between 96.3 % to 96.7 %. Keywords: Bromide content, doxorubicin hydrochloride, hydrobromic acid (HBr), potentiometric titration, silver nitrate (AgNO3), Received 18 July 2013 Received in revised form 08 August 2013 Accepted 12 August 2013 *Address for correspondence: Dr. Divyesh K. Patel Sr. Executive-ADL Department, Sterling Biotech Limited, Vadodara-391421, Gujarat, India. E-mail: Divyesh.msc@gmail.com _________________________________________________________________________________________________________________________ INTRODUCTION Doxorubicin is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA, with the most serious adverse effect being life-threatening heart damage. It is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas [1]. The drug is administered intravenously, as the hydrochloride salt. Doxorubicin is commonly used to treat some leukemias and Hodgkin's lymphoma, as well as cancers of the bladder, breast, stomach, lung, ovaries, thyroid, soft tissue sarcoma, multiple myeloma, and others [2]. Doxorubicin interacts with DNA by intercalation and inhibition of macromolecular biosynthesis [3, 4]. This inhibits the progression of the enzyme topoisomerase II, which relaxes supercoils in DNA for transcription. Doxorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process of replication. The planar aromatic chromophore portion of the molecule intercalates between two base pairs of the DNA, while the six-membered daunosamine sugar sits in the minor groove and interacts with flanking base pairs immediately adjacent to the intercalation site, as evidenced by several crystal structures [5]. The manufacturing process of Doxorubicin involves use of Bromine or Hydrobromic acid and the final drug applied as its Hydrochloride salt (Fig. 1). Due to poisonous effect of Bromine its presence cannot be neglected. So during our research work we established a novel and precise Titrimetric procedure for quantitative determination of Bromide content in Doxorubicin Hydrochloride.