The Amazing Income Generation Power Of The E-64

The drug is an antitumor agent, employed extensively against several human malignancies like ovarian, lung, pancreatic, bladder, urothelial, and breast cancer. It is currently marketed as a lyophilized powder. The drug is also extensively employed as antiviral agent, enzyme inhibitor, immunosuppressive agent, and radiation-sensitizing agents. Gemcitabine is a prodrug that enters the cell by means of nucleoside transporters and becomes active through an intracellular transformation catalyzed by deoxycytidine kinase to its diphosphate and triphosphate derivatives. The triphosphate derivative is incorporated into the DNA strand, inhibiting thymidylate synthetase which inhibits DNA synthesis and chain elongation, contributing to the antineoplastic activity of the drug. The diphosphate derivative inhibits ribonucleotide reductase, the enzyme responsible for catalyzing synthesis of deoxynucleoside-triphosphate JQ1 order required for DNA synthesis. Gemcitabine triphosphate competes with endogenous nucleoside triphosphate for incorporation into DNA [1�C3]. Figure 1 Chemical structures of gemcitabine (1) and theophylline (2). A literature survey reveals that only a few methods based on ultraviolet spectroscopy [4], HPTLC [5], and HPLC [6�C13] are available for determination of drug in formulation. Although several HPLC [14�C22] and LC-MS/MS [23�C28] methods have been reported for estimation of drug and its metabolites in biological fluids, these methods [23�C28] are complicated, costly, and time consuming R428 supplier in comparison to a simple HPLC-UV method. A few stability indicating that HPLC methods [3, 11, 12] have been reported, which provides variable level of degradation of gemcitabine. Jansen et al. [3] reported the separation and identification of degraded product of gemcitabine in acidic stress condition. Mastanamma et al. [11] and Kudikala et al. [12] have reported the validated stability indicating method which can separate the hydrolytic degraded product of gemcitabine. However, to the best of our knowledge none of the HPLC method reported the oxidative degraded product of gemcitabine. Previously published methods for formulation are less robust and need more investigations for method development and validation. Stability-indicating methods have to demonstrate that E-64 they are specific, which involves evaluating the drug in the presence of its degradation products [29]. The present investigation describes a simple, rapid, accurate, precise, robust stability indicating RP-HPLC method for the determination of gemcitabine for dosage forms. The robustness of the method was studied using 24 factorial design. The method was validated as per the ICH guidelines. 2. Experimental 2.1. Chemicals and Reagents The reference sample of gemcitabine was supplied by M/s Shilpa Medicare Limited, Raichur, India. Theophylline (2) was received as gift sample from Hetero Pharmaceutical Ltd., Hyderabad, India.