Development and validation of a rapid and sensitive UPLC-MS/MS method for determination of uracil and dihydrouracil in human plasma

Journal of Pharmaceutical and Biomedical Analysis

Volumn 126, Issue , 2016, Pages 75-82

  Jacobs, Bart A W ^a   Rosing, Hilde ^a   de Vries, Niels ^a   Meulendijks, Didier ^a   Henricks, Linda M ^a   Schellens, Jan H M ^a,b   Beijnen, Jos H ^a,b  

^a NETHERLANDS CANCER INSTITUTE   (Netherlands)

^b UTRECHT UNIVERSITY   (Netherlands)

Author keywords

5 Fluorouracil; Capecitabine; Dihydropyrimidine dehydrogenase; Dihydrouracil; UPLC MS MS; Uracil

Indexed keywords

CAPECITABINE; CARBON 13; DIHYDROURACIL; NITROGEN 15; URACIL; DIHYDROPYRIMIDINE DEHYDROGENASE;

ARTICLE; BLOOD ANALYSIS; COLORECTAL CANCER; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG STABILITY; ELECTROSPRAY MASS SPECTROMETRY; ENVIRONMENTAL TEMPERATURE; HUMAN; LIQUID CHROMATOGRAPH; MASS SPECTROMETER; MEASUREMENT ACCURACY; PHASE 1 CLINICAL TRIAL (TOPIC); PRECIPITATION; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; SENSITIVITY AND SPECIFICITY; STANDARD; TANDEM MASS SPECTROMETRY; ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY; VALIDATION STUDY; ANALOGS AND DERIVATIVES; BLOOD; COMPLICATION; DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; METABOLISM; PROCEDURES; TEMPERATURE; TIME FACTOR;

CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY; DIHYDROURACIL DEHYDROGENASE (NADP); HUMANS; TANDEM MASS SPECTROMETRY; TEMPERATURE; TIME FACTORS; URACIL;

EID: 84966280672     PISSN: 07317085     EISSN: 1873264X     Source Type: Journal    
DOI: 10.1016/j.jpba.2016.04.039     Document Type: Article

References (44)

1. Heggie G.D., Sommadossi J.P., Cross D.S., Huster W.J., Diasio R.B. Clinical pharmacokinetics of 5-fluorouracil and its metabolites in plasma, urine, and bile. Cancer Res. 1987, 47:2203-2206.
2. Thorn C.F., Marsh S., Carrillo M.W., McLeod H.L., Klein T.E., Altman R.B. PharmGKB summary: fluoropyrimidine pathways. Pharmacogenet. Genomics 2011, 21:237-242. 10.1097/FPC.0b013e328348c6f2.
3. 14C-labelled drug. Invest. New Drugs 1999, 17:49-56.
4. Twelves C., Wong A., Nowacki M.P., Abt M., Burris H., Carrato A., Cassidy J., Cervantes A., Fagerberg J., Georgoulias V., Husseini F., Jodrell D., Koralewski P., Kröning H., Maroun J., Marschner N., McKendrick J., Pawlicki M., Rosso R., Schüller J., Seitz J.-F., Stabuc B., Tujakowski J., van Hazel G., Zaluski J., Scheithauer W. Capecitabine as adjuvant treatment for stage III colon cancer. N. Engl. J. Med. 2005, 352:2696-2704. 10.1056/NEJMoa043116.
5. Mikhail S.E., Sun J.F., Marshall J.L. Safety of capecitabine: a review. Expert Opin. Drug Saf. 2010, 9:831-841. 10.1517/14740338.2010.511610.
6. Pluim D., Jacobs B.A.W., Deenen M.J., Ruijter A.E.M., van Geel R.M.J.M., Burylo A.M., Meulendijks D., Beijnen J.H., Schellens J.H.M. Improved pharmacodynamic assay for dihydropyrimidine dehydrogenase activity in peripheral blood mononuclear cells. Bioanalysis 2015, 7:519-529. 10.4155/bio.14.304.
7. Pluim D., Jacobs B.A.W., Krähenbühl M.D., Ruijter A.E.M., Beijnen J.H., Schellens J.H.M. Correction of peripheral blood mononuclear cell cytosolic protein for hemoglobin contamination. Anal. Bioanal. Chem. 2013, 405:2391-2395.
8. van Kuilenburg A.B.P., Van Lenthe H., Tromp A., Veltman P.C., Van Gennip A.H. Pitfalls in the diagnosis of patients with a partial dihydropyrimidine dehydrogenase deficiency. Clin. Chem. 2000, 46:9-17.
9. Fleming R.A., Milano G., Thyss A., Etienne M.C., Renée N., Schneider M., Demard F. Correlation between dihydropyrimidine dehydrogenase activity in peripheral mononuclear cells and systemic clearance of fluorouracil in cancer patients. Cancer Res. 1992, 52:2899-2902.
10. van Kuilenburg A.B.P., Meinsma R., Zoetekouw L., Van Gennip A.H. Increased risk of grade IV neutropenia after administration of 5-fluorouracil due to a dihydropyrimidine dehydrogenase deficiency: High prevalence of the IVS14 + 1G > A mutation. Int. J. Cancer 2002, 101:253-258.
11. Milano G., Etienne M.C., Pierrefite V., Barberi-Heyob M., Deporte-Fety R., Renée N. Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity. Br. J. Cancer 1999, 79:627-630. 10.1038/sj.bjc.6690098.
12. Van Kuilenburg A.B.P., Haasjes J., Richel D.J., Zoetekouw L., Van Lenthe H., de Abreu R.A., Maring J.G., Vreken P., van Gennip A.H. Clinical implications of dihydropyrimidine dehydrogenase (DPD) deficiency in patients with severe 5-fluorouracil-associated toxicity: Identification of new mutations in the DPD gene. Clin. Cancer Res. 2000, 6:4705-4712.
13. Büchel B., Rhyn P., Schürch S., Bühr C., Amstutz U., Largiadèr C.R. LC-MS/MS method for simultaneous analysis of uracil, 5,6-dihydrouracil, 5-fluorouracil and 5-fluoro-5,6-dihydrouracil in human plasma for therapeutic drug monitoring and toxicity prediction in cancer patients. Biomed. Chromatogr. 2013, 27:7-16.
14. Jiang H., Jiang J., Hu P., Hu Y. Measurement of endogenous uracil and dihydrouracil in plasma and urine of normal subjects by liquid chromatography-tandem mass spectrometry. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2002, 769:169-176.
15. van Staveren M.C., Theeuwes-Oonk B., Guchelaar H.-J., van Kuilenburg A.B.P., Maring J.G. Pharmacokinetics of orally administered uracil in healthy volunteers and in DPD-deficient patients, a possible tool for screening of DPD deficiency. Cancer Chemother. Pharmacol. 2011, 68:1611-1617. 10.1007/s00280-011-1661-5.
16. Déporte R., Amiand M., Moreau A., Charbonnel C., Campion L. High-performance liquid chromatographic assay with UV detection for measurement of dihydrouracil/uracil ratio in plasma. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2006, 834:170-177. 10.1016/j.jchromb.2006.02.046.
17. Svobaite R., Solassol I., Pinguet F., Ivanauskas L., Brès J., Bressolle F.M.M. HPLC with UV or mass spectrometric detection for quantifying endogenous uracil and dihydrouracil in human plasma. Clin. Chem. 2008, 54:1463-1472. 10.1373/clinchem.2007.102251.
18. Kristensen M.H., Pedersen P., Mejer J. The value of dihydrouracil/uracil plasma ratios in predicting 5-fluorouracil-related toxicity in colorectal cancer patients. J. Int. Med. Res. 2010, 38:1313-1323.
19. Coudoré F., Roche D., Lefeuvre S., Faussot D., Billaud E.M., Loriot M.-A., Beaune P. Validation of an ultra-high performance liquid chromatography tandem mass spectrometric method for quantifying uracil and 5 6-dihydrouracil in human plasma. J. Chromatogr. Sci. 2012, 50:877-884. 10.1093/chromsci/bms085.
20. Garg M.B., Sevester J.C., Sakoff J.A., Ackland S.P. Simple liquid chromatographic method for the determination of uracil and dihydrouracil plasma levels: a potential pretreatment predictor of 5-fluorouracil toxicity. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2002, 774:223-230.
21. Remaud G., Boisdron-Celle M., Hameline C., Morel A., Gamelin E. An accurate dihydrouracil/uracil determination using improved high performance liquid chromatography method for preventing fluoropyrimidines-related toxicity in clinical practice. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2005, 823:98-107. 10.1016/j.jchromb.2005.05.044.
22. Ciccolini J., Mercier C., Blachon M.-F., Favre R., Durand A., Lacarelle B. A simple and rapid high-performance liquid chromatographic (HPLC) method for 5-fluorouracil (5-FU) assay in plasma and possible detection of patients with impaired dihydropyrimidine dehydrogenase (DPD) activity. J. Clin. Pharm. Ther. 2004, 29:307-315. 10.1111/j.1365-2710.2004.00569.x.
23. Gamelin E., Boisdron-Celle M., Larra F., Robert J. A simple chromatographic method for the analysis of pyrimidines and their dihydrogenated metabolites. J. Liq. Chromatogr. Relat. Technol. 1997, 20:3155-3172. 10.1080/10826079708000481.
24. Hahn R.Z., Galarza A.F.A., Schneider A., Antunes M.V., Schwartsmann G., Linden R. Improved determination of uracil and dihydrouracil in plasma after a loading oral dose of uracil using high-performance liquid chromatography with photodiode array detection and porous graphitic carbon stationary phase. Clin. Biochem. 2015, 48:915-918.
25. César I.C., Cunha-Júnior G.F., Duarte Byrro R.M., Vaz Coelho L.G., Pianetti G.A. A rapid HPLC-ESI-MS/MS method for determination of dihydrouracil/uracil ratio in plasma: evaluation of toxicity to 5-flurouracil in patients with gastrointestinal cancer. Ther. Drug Monit. 2012, 34:59-66.
26. Sparidans R.W., Bosch T.M., Jörger M., Schellens J.H.M., Beijnen J.H. Liquid chromatography-tandem mass spectrometric assay for the analysis of uracil, 5,6-dihydrouracil and beta-ureidopropionic acid in urine for the measurement of the activities of the pyrimidine catabolic enzymes. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2006, 839:45-53. 10.1016/j.jchromb.2006.02.016.
27. van Lenthe H., van Kuilenburg A.B.P., Ito T., Bootsma A.H., van Cruchten A., Wada Y., van Gennip A.H. Defects in pyrimidine degradation identified by HPLC-electrospray tandem mass spectrometry of urine specimens or urine-soaked filter paper strips. Clin. Chem. 2000, 46:1916-1922.
28. Hartmann S., Okun J.G., Schmidt C., Langhans C.-D., Garbade S.F., Burgard P., Haas D., Oliver Sass J., Nyhan W.L., Hoffmann G.F. Comprehensive detection of disorders of purine and pyrimidine metabolism by HPLC with electrospray ionization tandem mass spectrometry. Clin. Chem. 2006, 52:1127-1137. 10.1373/clinchem.2005.058842.
29. Sun Q. Urine Pyrimidine Metabolite Determination by HPLC Tandem Mass Spectrometry. Methods Mol. Biol. 2016, 1378:237-242. 10.1007/978-1-4939-3182-8_25.
30. Schmidt C., Hofmann U., Kohlmüller D., Mürdter T., Zanger U.M., Schwab M., Hoffmann G.F. Comprehensive analysis of pyrimidine metabolism in 450 children with unspecific neurological symptoms using high-pressure liquid chromatography-electrospray ionization tandem mass spectrometry. J. Inherit. Metab. Dis. 2005, 28:1109-1122. 10.1007/s10545-005-0133-7.
31. Hofmann U., Schwab M., Seefried S., Marx C., Zanger U.M., Eichelbaum M., Mürdter T.E. Sensitive method for the quantification of urinary pyrimidine metabolites in healthy adults by gas chromatography-tandem mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2003, 791:371-380.
32. Carlsson G., Odin E., Gustavsson B., Wettergren Y. Pretherapeutic uracil and dihydrouracil levels in saliva of colorectal cancer patients are associated with toxicity during adjuvant 5-fluorouracil-based chemotherapy. Cancer Chemother. Pharmacol. 2014, 74:757-763.
33. Kristensen M.H., Weidinger M., Bzorek M., Pedersen P.L., Mejer J. Correlation between thymidylate synthase gene variants, RNA and protein levels in primary colorectal adenocarcinomas. J. Int. Med. Res. 2010, 38:484-497.
34. Gamelin M., Boisdron-Celle M., Guérin-Meyer V., Delva R., Lortholary A., Genevieve F., Larra F., Ifrah N., Robert J. Correlation between uracil and dihydrouracil plasma ratio, fluorouracil (5-FU) pharmacokinetic parameters, and tolerance in patients with advanced colorectal cancer: A potential interest for predicting 5-FU toxicity and determining optimal 5-FU dosage. J. Clin. Oncol. 1999, 17:1105-1110.
35. Jiang H., Lu J., Jiang J., Hu P. Important role of the dihydrouracil/uracil ratio in marked interpatient variations of fluoropyrimidine pharmacokinetics and pharmacodynamics. J. Clin. Pharmacol. 2004, 44:1260-1272. 10.1177/0091270004268911.
36. Sistonen J., Büchel B., Froehlich T.K., Kummer D., Fontana S., Joerger M., van Kuilenburg A.B.P., Largiadèr C.R. Predicting 5-fluorouracil toxicity: DPD genotype and 5,6-dihydrouracil:uracil ratio. Pharmacogenomics 2014, 15:1653-1666. 10.2217/pgs.14.126.
37. Zhou Z.W., Wang G.Q., Sen Wan D., Lu Z.H., Chen Y.B., Li S., Chen G., Pan Z.Z. The dihydrouracil/uracil ratios in plasma and toxicities of 5-fluorouracil-based adjuvant chemotherapy in colorectal cancer patients. Chemotherapy 2007, 53:127-131. 10.1159/000099984.
38. Boisdron-Celle M., Remaud G., Traore S., Poirier A.L., Gamelin L., Morel A., Gamelin E. 5-Fluorouracil-related severe toxicity: a comparison of different methods for the pretherapeutic detection of dihydropyrimidine dehydrogenase deficiency. Cancer Lett. 2007, 249:271-282. 10.1016/j.canlet.2006.09.006.
39. Maring J.G., Schouten L., Greijdanus B., de Vries E.G.E., Uges D.R.A. A simple and sensitive fully validated HPLC-UV method for the determination of 5-fluorouracil and its metabolite 5,6-dihydrofluorouracil in plasma. Ther. Drug Monit. 2005, 27:25-30.
40. European Medicines Agency, Committee for Medicinal Products for Human Use, 2011 (accessed 22.11.2015). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/08/WC500109686.pdf.
41. US Food and Drug Administration, Department of Health and Human Services, 2001 (accessed 22.11.2015). http://www.fda.gov/downloads/Drugs/Guidances/ucm070107.pdf.
42. Traut T.W. Physiological concentrations of purines and pyrimidines. Mol. Cell. Biochem. 1994, 140:1-22. 10.1007/BF00928361.
43. Temmink O.H., de Bruin M., Laan A.C., Turksma A.W., Cricca S., Masterson A.J., Noordhuis P., Peters G.J. The role of thymidine phosphorylase and uridine phosphorylase in (fluoro)pyrimidine metabolism in peripheral blood mononuclear cells. Int. J. Biochem. Cell Biol. 2006, 38:1759-1765. 10.1016/j.biocel.2006.04.007.
44. Van Kuilenburg A.B.P., van Lenthe H., Blom M.J., Mul E.P., Van Gennip A.H. Profound variation in dihydropyrimidine dehydrogenase activity in human blood cells: major implications for the detection of partly deficient patients. Br. J. Cancer. 1999, 79:620-626. 10.1038/sj.bjc.6690097.