DETERMINATION OF CAPECITABINE-AN ANTICANCER DRUG IN DRIED BLOOD SPOT BY LC-ESI-MS/MS
Keywords:
Capecitabine, Capecitabine-d11, Dried blood spot, Selective, LC-MSMS, Post-column infusionAbstract
Objective: Capecitabine (Cape), the first oral prodrug which belongs to the group of fluoro pyrimidines is the most frequently prescribed anticancer drug for the treatment of metastatic breast and colorectal cancers. The article describes a selective and robust method for determination of Cape in dried blood spots (DBS) by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Methods: Cape fortified DBS was punched and extracted with ethyl acetate using capecitabine-d11 as the internal standard (IS). Chromatographic separation of Cape and IS from endogenous matrix was performed on Phenomenex Gemini C18 (150 × 4.6 mm, 5mm) column under isocratic condition using acetonitrile: 2 mmol ammonium formate (pH 3.0, adjusted with 0.1 % formic acid) (80:20, v/v) as the mobile phase. Detection and quantification were carried on a triple quadrupole mass spectrometer, using electro spray ionization technique in the positive ionization mode.
Results: The method was established over a concentration range of 10-10000 ng/ml. Accuracy, precision, selectivity, recovery, matrix effect and stability of the analyte were also estimated and the results were within the acceptance criteria. Further, precise results were obtained using an optimum spot volume of 10 µl with good spot homogeneity. Blood samples with hematocrit values varying from 24 % to 45 % gave acceptable results with good accuracy and precision.
Conclusion: The efficiency of dried blood spot sample preparation, short analysis time and high selectivity permits estimation of Cape in a small blood volume. The validation results suggest that the method is precise, accurate, and reproducible and can be useful in therapeutic drug monitoring of Cape.
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References
Walko CM, Lindley C. Capecitabine: a review. Clin Ther 2005;27:23-44.
Milano G, Schellens JHM. Pyrimidine antimetabolites. In: Schellens JHM, McLeod HL, Newell DR. eds. Cancer Clinical Pharmacology. Oxford: University Press; 2005. p. 51-62.
Hirsch BR, Zafar SY. Capecitabine in the management of colorectal cancer. Cancer Manag Res 2011;3:79-89.
Ãlvarez P, Marchal JA, Boulaiz H, Carrillo E, Vélez C, RodrÃguez-Serrano F, et al. 5-Fluorouracil derivatives: a patent review. Expert Opin Ther Pat 2012;22:107-23.
Reigner B, Blesch K, Weidekamm E. Clinical pharmacokinetics of capecitabine. Clin Pharmacokinet 2001;40:85-104.
Mei JV, Alexander JR, Adam BW, Hannon WH. Use of filter paper for the collection and analysis of human whole blood specimens. J Nutr 2001;131:1631S-6S.
Meesters RJ, Hooff GP. State-of-the-art dried blood spot analysis: an overview of recent advances and future trends. Bioanalysis 2013;5:2187-208.
Meesters RJ, Hooff GP, Gruters R, van Kampen JJ, Luider TM. Incurred sample reanalysis comparison of dried blood spots and plasma samples on the measurement of lopinavir in clinical samples. Bioanalysis 2012;4:237-40.
Spooner N. A dried blood spot update: still an important bioanalytical technique? Bioanalysis 2013;5:879-83.
Farkouh A, Ettlinger D, Schueller J, Georgopoulos A, Scheithauer W, Czejka M. A rapid and simple HPLC assay for quantification of capecitabine for drug monitoring purposes. Anticancer Res 2010;30:5207-12.
Piorkowska E, Kaza M, Fitatiuk J, Szlaska I, Pawinski T, Rudzki PJ. Rapid and simplified HPLC-UV method with on-line wavelengths switching for determination of capecitabine in human plasma. Pharmazie 2014;69:500-5.
Guichard SM, Mayer I, Jodrell DI. Simultaneous determination of capecitabine and its metabolites by HPLC and mass spectrometry for preclinical and clinical studies. J Chromatogr B 2005;826:232-7.
Dhananjeyan MR, Liu J, Bykowski C, Trendel JA, Sarver JG, Andob H, et al. Rapid and simultaneous determination of capecitabine and its metabolites in mouse plasma, mouse serum, and in rabbit bile by high-performance liquid chromatography. J Chromatogr A 2007;1138:101-8.
Xu Y, Grem JL. Liquid chromatography–mass spectrometry method for the analysis of the anti-cancer agent capecitabine and its nucleoside metabolites in human plasma. J Chromatogr B 2003;783:273-85.
Siethoff C, Orth M, Ortling A, Brendel E, Redeker WW. Simultaneous determination of capecitabine and its metabolite 5-fluorouracil by column switching and liquid chromatographic/tandem mass spectrometry. J Mass Spectrom 2004;39:884-9.
Zufia L, Aldaz A, Giraldez J. Simple determination of capecitabine and its metabolites by liquid chromatography with ultraviolet detection in a single injection. J Chromatogr B 2004;809:51-8.
Salvador A, Millerioux L, Renou A. Simultaneous LC-MS-MS analysis of capecitabine and its metabolites (5’-deoxy-5-fluorocytidine, 5’-deoxy-5-fluorouridine, 5-fluorouracil) after off-line spe from human plasma. Chromatographia 2006;63:609-15.
Licea-Perez H, Wang S, Bowen C. Development of a sensitive and selective LC-MS/MS method for the determination of ï¡-fluoro-ï¢-alanine, 5-fluorouracil and capecitabine in human plasma. J Chromatogr B 2009;877:1040-6.
Montange D, Berard M, Demarchi M, Muret P, Piedoux S, Kantelipa JP, et al. An APCI LC-MS/MS method for routine determination of capecitabine and its metabolites in human plasma. J Mass Spectrom 2010;45:670-7.
Vainchtein LD, Rosing H, Schellens JHM, Beijnen JH. A new, validated HPLC-MS/MS method for the simultaneous determination of the anti-cancer agent capecitabine and its metabolites: 5’-deoxy-5-fluorocytidine, 5’-deoxy-5-fluorouridine, 5-fluorouracil and 5-fluorodihydrouracil, in human plasma. Biomed Chromatogr 2010;24:374-86.
Svobaite R, Solassol I, Pinguet F, Mazard T, Ivanauskas L, Ychou M, et al. A liquid chromatography-mass spectrometry method for the simultaneous determination of capecitabine, 5’-deoxy-5-fluorocytidine, 5’-deoxy-5-fluorouridine, 5-fluorouracil, and 5-fluorodihydrouracil in human plasma. J Liq Chromatogr Relat Technol 2010;33:1705-19.
Deenen MJ, Rosing H, Hillebrand MJ, Schellensa JHM, Beijnen JH. Quantitative determination of capecitabine and its six metabolites in human plasma using liquid chromatography coupled to electrospray tandem mass spectrometry. J Chromatogr B 2013;913-914:30-40.
Deng P, Ji C, Dai X, Zhong D, Ding L, Chen X. Simultaneous determination of capecitabine and its three nucleoside metabolites in human plasma by high-performance liquid chromatography–tandem mass spectrometry. J Chromatogr B 2015;989:71-9.
Gomez-Canela C, Cortes-Francisco N, Ventura F, Caixach J, Lacorte S. Liquid chromatography coupled to tandem mass spectrometry and high-resolution mass spectrometry as analytical tools to characterize multi-class cytostatic compounds. J Chromatogr A 2013;1276:78-94.
Negreira N, Mastroianni N, López de Alda M, Barceló D. Multianalyte determination of 24 cytostatics and metabolites by liquid chromatography–electrospray–tandem mass spectrometry and study of their stability and optimum storage conditions in aqueous solution. Talanta 2013;116:290-9.
FDA. Guidance for Industry: Bioanalytical Method Validation. U. S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research (CDER), and Center for Veterinary Medicine (CVM); 2001.
Shah PA, Sharma P, Shah JV, Sanyal M, Shrivastav PS. Simultaneous analysis of losartan, its active metabolite, and hydrochlorothiazide in human plasma by a UPLC-MS/MS method. Turk J Chem 2015;39:714-33.
Sharma P, Patel DP, Sanyal M, Berawala H, Guttikar S, Shrivastav PS. Simultaneous analysis of oxybutynin and its active metabolite N-desethyl oxybutynin in human plasma by stable isotope dilution LC-MS/MS to support a bioequivalence study. J Pharm Biomed Anal 2013;84:244-55.
Nijenhuis CM, Rosing H, Schellens JHM, Beijnen JH. Quantifying vemurafenib in dried blood spots using high-performance LC–MS/MS. Bioanalysis 2014;6:3215-24.
Timmerman P, White S, Cobb Z, de Vries R, Thomas E, van Baar B. Update of the EBF recommendation for the use of DBS in regulated bioanalysis integrating the conclusions from the EBF DBS-microsampling consortium. Bioanalysis 2013;5:2129-36.