BACKGROUND: 5-Fluorouracil (5-FU) is the most widely used chemotherapy drug, primarily against gastrointestinal, head and neck, and breast cancers. 5-FU has large pharmacokinetic variability resulting in unexpected toxicity or ineffective treatment. Therapeutic drug management of 5-FU minimizes toxicity and improves outcome. A nanoparticle-based immunoassay was developed to provide oncologists with a rapid, cost-effective tool for determining 5-FU plasma concentrations. METHODS: Monoclonal antibodies, bound to nanoparticles, were used to develop an immunoassay for the Olympus AU400. Assay precision, linearity, calibration stability, and limit of detection were run at multiple centers; interference, cross-reactivity, lower limit of quantitation and recovery at 1 center. Clinical samples collected from 4 cancer centers were analyzed for 5-FU concentrations by liquid chromatography-tandem mass spectrometry and compared with the immunoassay results. RESULTS: With calibrators from 0 to 1800 ng/mL 5-FU and autodilution, concentrations up to 9000 ng/mL could be determined. Time to first result was 10 minutes, and 400 samples per hour could be quantitated from a standard curve stored for >30 days. Imprecision across all laboratories was <5%, and the assay was linear upon dilution over the entire range. Cross-reactivities for dihydro-5-FU, uracil, capecitabine, and tegafur were <1%, 9.9%, 0.05%, and 0.23%, respectively. The limit of detection was 52 ng/mL with a lower limit of quantitation of 86 ng/mL. Assay results of clinical samples (93-1774 ng/mL) correlated with liquid chromatography-tandem mass spectrometry results: (R = 0.9860, slope 1.035, intercept 10.87 ng/mL). CONCLUSIONS: This novel immunoassay is suitable for quantitating 5-FU plasma concentrations with advantages of speed, small sample size, minimal sample pretreatment, and application on automated instrumentation. These advantages enable efficient therapeutic drug management of 5-FU in clinical practice.
BACKGROUND:5-Fluorouracil (5-FU) is the most widely used chemotherapy drug, primarily against gastrointestinal, head and neck, and breast cancers. 5-FU has large pharmacokinetic variability resulting in unexpected toxicity or ineffective treatment. Therapeutic drug management of 5-FU minimizes toxicity and improves outcome. A nanoparticle-based immunoassay was developed to provide oncologists with a rapid, cost-effective tool for determining 5-FU plasma concentrations. METHODS: Monoclonal antibodies, bound to nanoparticles, were used to develop an immunoassay for the Olympus AU400. Assay precision, linearity, calibration stability, and limit of detection were run at multiple centers; interference, cross-reactivity, lower limit of quantitation and recovery at 1 center. Clinical samples collected from 4 cancer centers were analyzed for 5-FU concentrations by liquid chromatography-tandem mass spectrometry and compared with the immunoassay results. RESULTS: With calibrators from 0 to 1800 ng/mL 5-FU and autodilution, concentrations up to 9000 ng/mL could be determined. Time to first result was 10 minutes, and 400 samples per hour could be quantitated from a standard curve stored for >30 days. Imprecision across all laboratories was <5%, and the assay was linear upon dilution over the entire range. Cross-reactivities for dihydro-5-FU, uracil, capecitabine, and tegafur were <1%, 9.9%, 0.05%, and 0.23%, respectively. The limit of detection was 52 ng/mL with a lower limit of quantitation of 86 ng/mL. Assay results of clinical samples (93-1774 ng/mL) correlated with liquid chromatography-tandem mass spectrometry results: (R = 0.9860, slope 1.035, intercept 10.87 ng/mL). CONCLUSIONS: This novel immunoassay is suitable for quantitating 5-FU plasma concentrations with advantages of speed, small sample size, minimal sample pretreatment, and application on automated instrumentation. These advantages enable efficient therapeutic drug management of 5-FU in clinical practice.
Authors: Shann S Yu; Ryan A Ortega; Brendan W Reagan; John A McPherson; Hak-Joon Sung; Todd D Giorgio Journal: Wiley Interdiscip Rev Nanomed Nanobiotechnol Date: 2011-08-10
Authors: Jan H Beumer; Edward Chu; Carmen Allegra; Yusuke Tanigawara; Gerard Milano; Robert Diasio; Tae Won Kim; Ron H Mathijssen; Li Zhang; Dirk Arnold; Katsuki Muneoka; Narikazu Boku; Markus Joerger Journal: Clin Pharmacol Ther Date: 2018-09-11 Impact factor: 6.875
Authors: Wolfgang Hohenforst-Schmidt; Paul Zarogoulidis; Georgia Pitsiou; Bernd Linsmeier; Drosos Tsavlis; Ioannis Kioumis; Eleni Papadaki; Lutz Freitag; Theodora Tsiouda; J Francis Turner; Robert Browning; Michael Simoff; Nikolaos Sachpekidis; Kosmas Tsakiridis; Bojan Zaric; Lonny Yarmus; Sofia Baka; Grigoris Stratakos; Harald Rittger Journal: J Cancer Date: 2016-01-13 Impact factor: 4.207
Authors: Karoline Freeman; Mark P Saunders; Olalekan A Uthman; Sian Taylor-Phillips; Martin Connock; Rachel Court; Tara Gurung; Paul Sutcliffe; Aileen Clarke Journal: BMC Cancer Date: 2016-07-25 Impact factor: 4.430