Development and Validation of HPLC and HPTLC Methods for Therapeutic Drug Monitoring of Capecitabine in Colorectal Cancer Patients

Abstract

Capecitabine is a prodrug of 5-fluorouracil, employed as a monotherapy or combination chemotherapy agent for treatment of colorectal cancer. Combination therapy of capecitabine consists of oxaliplatin, and hence, it becomes essential to determine that co-administration does not affect its metabolism. High-performance liquid chromatography and high-performance thin-layer chromatography methods were developed and validated to determine the plasma concentration of capecitabine. In this study, blood samples from 12 patients with colorectal cancer were collected and analyzed by both methods with a reference internal standard. Two groups consisting of six patients each were formed: the first group was treated with capecitabine monotherapy, the second group with capecitabine + oxaliplatin combination therapy. The results of analysis from both the methods indicated that there is no significant drug–drug interaction. The co-administration of oxaliplatin did not affect the metabolism of capecitabine. Both assay methods were compared for their sensitivity, robustness and specificity. It was found that both the assay methods were suitable for therapeutic drug monitoring of capecitabine.

Capecitabine inhibits epithelial‑to‑mesenchymal transition and proliferation of colorectal cancer cells by mediating the RANK/RANKL pathway

“…At present, treatment for CRC mainly consists of surgery supplemented by chemotherapy (5-fluorouracil, oxaliplatin, irinotecan and capecitabine), which can achieve satisfactory therapeutic effects ( 7 – 9 ). However, a lack of effective treatment methods remain for patients with advanced-stage CRC tumors ( 7 ).…”

“…To increase the therapeutic efficacy of chemotherapy in colorectal cancer, the search for downstream effectors is required. In particular, capecitabine is typically administered as a combinational chemotherapy (with surgery) or as a monotherapy for CRC treatment ( 9 ). It preferentially generates 5-flurouracil (5-FU) which represents a well-established treatment method ( 12 ).…”

A small-scale method of sample preparation suitable for simultaneous HPLC-UV assay of capecitabine and its 5’-DFCR metabolite in mouse blood plasma

“…The aim of the present study was to further verify the implementation of the protein precipitation method using the antineoplastic agent capecitabine and its first metabolite, 5′-deoxy-5-fluorocytidine (5′-DFCR). In this work, the qualitative and quantitative composition of each biological specimen was accurately assessed using high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection (Thorat, Chikhale, Tajne, 2019;Vijaya Jyothi et al, 2018;Hassanlou et al, 2016;Piórkowska et al, 2014;Komarov et al, 2014;Farkouh et al, 2010;Zufı á, Aldaz, Giráldez, 2004).…”

Current Status of Therapeutic Drug Monitoring of 5-Fluorouracil Prodrugs

“…In addition, recent studies have reported a relationship between drug exposure, toxicity and efficacy (8). In previous reports, the response rate was significantly improved and adverse events were reduced for patients who underwent TDM-based 5-FU dose adjustment compared with patients treated with conventional 5-FU administration (9)(10)(11)(12). Appropriate adjustment of the 5-FU blood concentration can improve both the safety and efficacy of treatment.…”