HPLC Assay Method Development and Validation for Quantification of Capecitabine in Tablets and Forced Degradation Samples

Abstract

A simple, rapid, accurate and stability indicating RP-HPLC method was developed for the determination of Capecitabine in pure and tablet dosage form. The mobile phase consisting of 0.1% aqcetic acid, methanol and acetonitrile in the ratio of 35:60:5 v/v. The Inertsil ODS (octadecyl silane), C18, 3V, 250 x 4.6 mm, 5µm with UV detection 304 nm was used. The retention time was found to be 6.4 minutes. The method was statistically validated for accuracy, linearity, precision, robustness, specificity and range. The method was found linear over the concentration range of 50-150 µg/ml. The recovery studies of dosage form were also carried out and analyzed; the % relative standard deviation (RSD) from recovery studies was found to be within limits. The specificity of the method was ascertained by forced degradation studies by acid, alkali hydrolysis and oxidation. About 35% of drug is degraded in acidic medium and less than that in alkaline and oxidative conditions. Due to simplicity, rapidity and accuracy of the method, the method will be useful for routine analysis and checking purity of capecitabine tablet. The method further can be investigated for pharmacokinetic and biopharmaceutical analysis.

Study of loss of the active principle capecitabine and cytotoxic activity in preparation intended for administration in liquid form

“…The assays were performed in triplicate, and the results for both analyzed cell lines are presented in Table 3. The UFLC method used in this research has been employed in other studies to determine the concentration of CAP in samples obtained from dissolved tablets [13,18,19], and in plasma samples [4,20,21]. In all of them, UFLC proved to be a suitable method with proven e ciency for determining the concentration of the prodrug CAP in various samples.…”

“…Moreover, in many previously described studies, it is known that the prodrug CAP is converted into 5-FU through at least three metabolic steps after intestinal absorption, namely: starting with the action of hepatic carboxylesterases that convert CAP into 5'-DFCR, which is then converted to 5'-DFUR by cytidine deaminase present in high concentrations in the liver, plasma, and tumor tissue; and nally, 5'-DFUR is converted into the active drug 5-FU by the action of thymidine phosphorylase, which is found in higher quantities in solid tumors compared to adjacent normal tissues, and thus exerts its cytotoxic effect on cancer cells [20,28]. However, from the results obtained in this study, it is observed that the metabolic pathway for converting CAP to 5-FU may not be exclusively dependent on the action of hepatic carboxylesterases, suggesting that these enzymes may also be present in tumor cells, or that there may be other pathway(s) in tumor cells capable of promoting the conversion of CAP to 5-FU, or even to another metabolite(s) of CAP that possess signi cant cytotoxic effects on MCF-7 and MDA-MB-231 cell lines.…”

Method Validation of Capecitabine in Api and Pharmaceutical Dosage From by Uv Spectrophotometric Method

“…It acts as a prodrug that was triggered by the enzyme thymidine phosphorylase to act on tumor cells by its cytotoxic moiety, and fluorouracil (FU). The active moiety of capecitabine said to be "targeted" against the cancerous cells [2]. The elimination half-life of both capecitabine and 5-FU is about 0.89 h, with more than 70% of the administered dose recovered in urine, largely as a metabolite of 5-FU the absolute bioavailability of capecitabine is 42%.…”

Carbon nanotube/polyurethane modified hollow fiber‐pencil graphite electrode for in situ concentration and electrochemical quantification of anticancer drugs Capecitabine and Erlotinib

“…Liquid chromatography is a rapid and simple method for studying drugs in pharmaceutical and clinical samples, but they need expensive devices and high purity solvents, which can restrict their use . Also the electrochemical methods can be seen in the literature because of their comfortable properties such as short analysis time, low cost, and sensitivity.…”