Determination Of Capecitabine Research Articles

Determination of Capecitabine and Its Metabolites in Plasma of Egyptian Colorectal Cancer Patients

The incidence of colorectal cancer (CRC) is increasing worldwide. It has variable signs and symptoms starting from changes in bowel habit to nausea and vomiting. Chemotherapeutic agents are often prescribed in CRC such as Capecitabine (CCB) and 5-Fluorouracil (FU). CCB is the prodrug of FU in oral dosage form, which makes it preferable by physicians, since no hospitalization is needed for drug administration. CCB is activated to FU in a three-step reaction producing 5′-deoxy-5-fluorocytidine (DFCR) (by carboxylesterase (CES) enzyme), then 5′-deoxy-5-fluorouridine (DFUR) (by cytidine deaminase (CDD) enzyme) and finally FU (by thymidine phosphorylase (TP) enzyme), the active form, which is later deactivated to give 5,6-dihydro-5-fluorouracil (DHFU). Different patients exhibit variable drug responses and adverse in response to CCB therapy, despite being treated by the same dose, which could be attributed to the occurrence of different possible enzyme single nucleotide polymorphisms (SNPs) along the activation and deactivation pathways of CCB. The most commonly occurring toxicities in CCB therapy are hand-foot syndrome and diarrhea. This study aims at developing and validating a new method for the simultaneous determination of CCB and its metabolites by HPLC-UV, followed by a correlation study with the toxicities occurring during therapy, where predictions of toxicity could be based on metabolites’ levels instead of the tedious process of genotyping. A new superior analytical method was optimized by a quality-by-design approach using DryLab® 2000 software achieving a baseline resolution of the six analytes within the least possible gradient time of 10 min. The method also showed linearity (in a range from 1 to 500 μg/mL), accuracy, precision and robustness upon validation: The LOD was found to be 3.0 ng/mL for DHFU and CCB, and 0.3 ng/mL for DFUR, DFCR and FU. The LOQ was found to be 10.0 ng/mL for DHFU and CCB, and 1.0 ng/mL for DFUR, DFCR and FU. The clinical results showed a positive correlation between the concentration of DFCR and mucositis and between the concentration of DFUR and hand-foot syndrome, confirming that this technique could be used for predicting such toxicities.

Silver nanoparticles-tragacanth gel as a green membrane for effective extraction and determination of capecitabine.

A novel eco-friendly and effective electromembrane extraction method combining high-performance liquid chromatography with UV detection was developed for the enrichment and determination of capecitabine. Tragacanth-silver nanoparticles conjugated gel was prepared by dissolving the tragacanth powder in synthesized silver nanoparticles solution and was used as a green membrane in electromembrane extraction. The porosity and presence of silver nanoparticles in the gel were characterized by field emission scanning electron microscopy. This new electromembrane extraction approachuses neither organic solvent nor carrier agents to extract the target analyte. The best electromembrane extraction efficiency was obtained by using 4.0mm membrane gel thickness containing 2.5% w/v of tragacanth gum, donor phase pH=5.0, acceptor phase pH=3.0, applied voltage 50 V, extraction time 20min, and agitation rate 500rpm. During method validation under the optimized conditions, good linearity dynamic range between 1 and 500ng/mL with the coefficient of determination (R2 )=0.998 was obtained. Limit of detection and Limit of quantitation were estimated to be 0.84 and 1.0ng/mL, respectively. Finally, the applicability of this method in real samples was confirmed by an acceptable performance in extraction and determination of capecitabine in human plasma samples.

METHOD VALIDATION OF CAPECITABINE IN API AND PHARMACEUTICAL DOSAGE FROM BY UV SPECTROPHOTOMETRIC METHOD

Objective: The simple, rapid spectrophotometric method was developed for the determination of capecitabine, an anticancer drug, in pharmaceutical formulations. Among the approaches, most commonly used targeted mechanism is pH-dependent delivery system which is based on pH gradient of the gastrointestinal tract (GIT) that increases progressively from the stomach.
 Methods: The focus of the present study is to similarize the capecitabine drug in bulk form with the marketed tablet (Capegard 500) on the simple, accurate, and precise manner by UV spectrophotometer.
 Results: Beer’s law was obeyed over a concentration range of 5–30 μg/mL in HCl at pH 1.2 and in phosphate buffer at pH 6.8 and 7.4. The linear regression equations of pure drug were found to be y = 0.0135x+0.2014, y = 0.0147x+0.2153, and y = 0. 0245x+0.1507 in HCl, phosphate buffer at 6.8 and 7.4, respectively, whereas the linear regression equations of marketed tablet were found to be y = 0.0158x+0.1964, y = 0.0192x+0.2261, and y = 0.015x+0.2032, respectively, and the three methods were validated as per the International Council for Harmonisation guideline (ICH).
 Conclusion: The regression values of every equation were found to be above 0.990 which indicated that all the equations were maintaining linearity.

Stopped‐flow chemiluminescence determination of the anticancer drug capecitabine: Application in pharmaceutical analysis and drug‐delivery systems

Capecitabine is a chemotherapeutic agent used for the treatment of patients with metastatic cancers. This study aimed at determining the drug capecitabine in a simple chemiluminescence (CL) system of acidic potassium permanganate using the stopped-flow injection technique. Statistical methods were used to detect optimum conditions. The method showed two linear calibration ranges from 6.7 × 10-6 to 6.7 × 10-5 mol L-1 and from 6.7 × 10-5 to 2.7 × 10-3 mol L-1 with a detection limit of 1.5 × 10-6 mol L-1 . Chitosan-modified magnetic nanoparticles were studied in the drug-delivery experiments. According to the pH sensitivity of chitosan and low pH values in tumour cells, the chitosan-coated magnetic nanoparticles could provide a good targeting drug-delivery system to tumour sites. To evaluate the applicability of the method, the capecitabine-loaded magnetic chitosan nanoparticles were synthesized with two different cross-linkers; loading and releasing rates of the drug were investigated using the proposed CL method and an ultraviolet-visible light spectrophotometric method (absorption at 305 nm). The results showed a good correlation between the two methods, and it was found that the synthesized chitosan-modified magnetic nanoparticles could be used for pH-dependent release of capecitabine in cancer cells. Moreover, determination of capecitabine in tablets and synthetic samples was performed.

A Validated Stability-Indicating HPTLC Method for the Estimation of Capecitabine in its Tablet Dosage Form

Background: Capecitabine is an orally available prodrug of 5-flurouracil used in the treatment of breast cancer, metastatic colorectal cancer and stage III colorectal cancer. Various studies have reported the HPLC, HPLC-MS, MS/MS methods for estimation of capecitabine. However, till date HPTLC method for estimation of capecitabine and its validation is not reported in tablet dosage form. Introduction: Presented study deals with the development and validation of stability indicating high performance thin layer chromatography method for the determination of Capecitabine in tablet dosage form. Methods: The method was developed using precoated HPTLC plates with silica gel 60 F254 as stationary phase and toluene-methanol the ratio of 7.5:2.5 v/v as the mobile phase. Capecitabine (RF 0.48 ± 0.03) and its degradation products were well resolved. The wavelength selected for study was 240 nm. The method was linear in the concentration range 50–550 ng/band with a correlation coefficient of 0.994. The repeatability for six samples was 1.25% RSD. The intraday and interday precisions were 1.46-1.71%RSD and 1.31-1.67% RSD, respectively. The accuracy (recovery) was found to be in the range of 99.10-101.23% with LOD and LOQ were found to be 0.650 and 1.765 mg/band. The mean content of drug in tablet dosage form was found to be 101.51% with a % RSD of 1.20. The drug was subjected to stress conditions such as hydrolysis, oxidation, photolysis, and heat. Results: Degradation products produced as a result of the stress conditions did not interfere with the detection of Capecitabine; therefore, the proposed technique can be considered stability-indicating. Capecitabine did not degrade under thermal and photolytic conditions but showed degradation under acidic and alkaline conditions with 15 and 11% decompositions respectively. Conclusion: The developed method was found to be facile, simple, specific, precise, and stabilityindicating. It can be employed for the routine analysis of capecitabine in tablet dosage form.

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

A simple, rapid accurate and forced degradation indicating RP-HPLC method was developed for the determination of Capecitabine in pure and tablet dosage form. The mobile phase used contains 0.1% Acetic acid, Methanol and Acetonitrile in the ratio of 35:60:5 v/v. The linearity range is found over the concentration range of 50-150µg/ml. The Inertsil ODS, C18, 3V, 250 x 4.6 mm, 5µm with UV detection 250 nm is used. The RT is found to be 6.4 mins. The method was statistically validated for accuracy, linearity, precision, robustness, specificity and range. Quantitative and recovery studies of the dosage form were also carried out and analyzed; the % 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 and about 35% of drug is degraded in acidic medium. 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.

Determination of capecitabine and its metabolites in plasma of Egyptian colorectal cancer patients

Determination of capecitabine and its metabolites in plasma of Egyptian colorectal cancer patients

STABILITY STUDY OF CAPECITABINE ACTIVE PHARMACEUTICAL INGREDIENT IN BULK DRUG AND PHARMACEUTICAL FORMULATION

A simple, precise, and accurate gradient reverse phase-LC method was developed for quantitative determination of capecitabine (CPT) drug sample and drug products in bulk samples and pharmaceutical dosage forms. Accelerated tests for stability evaluation were performed at 40°C ± 2°C and 75 ± 5% relative humidity (RH), according to the current official guidelines. The samples were kept in a climatic chamber for 6 mo in the aforementioned conditions. The samples were withdrawn from the climatic chamber and analyzed periodically (0, 3, and 6 mo) by HPLC on an Eclipse XDB-C18 column (250 × 4.6 mm i.d. particle size is 5 µm), using a mobile phase of 0.02 M ammonium formate containing formic acid to maintain pH at 4.0-acetonitrile with gradient, at a flow rate of 1.0 mL min−1. The UV detector was operated at 240 nm while column temperature was maintained at 40°C. The unknown impurity at relative retention time (RRT) of 0.26 min ranged from 0.02 to 1.90% on an area-percentage basis and has been observed in reverse phase-LC of CPT drug substance and drug product in accelerated test at two time points, initial (0 mo) and 6 mo. Chemically, the impurity was identified as 4-amino-1-(3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoro-pyrimidin-2(1H)-one. Utility of the developed method was examined by analyzing the tablets containing CPT. The results of analysis were supported by statistical parameters.