An Automated Nanoparticle-Based Homogeneous Immunoassay for Determining Docetaxel Concentrations in Plasma

• DOI: 10.1097/ftd.0b013e31829617ea
• Publication Date: 2013-11-21T09:16:53Z
• Authors: Daniel J. Cline; Hongxia Zhang; Gregory D. Lundell; Rebecca L. Harney; Hadia K. Riaz; Justin Jarrah; Yunying Li; Makoto Miyazaki; Jodi B. Courtney; Irina Baburina; Salvatore J. Sala...
• Keywords: Bioanalysis; Therapeutic index; Therapeutic Drug Monitoring

Background: Docetaxel (Taxotere) (DTX) is a widely used chemotherapy agent in many regimens for the treatment of solid tumors, example breast cancer, non–small cell lung gastric, prostate, and head neck cancers. This drug meets criteria therapeutic dose management, that it associated with high pharmacokinetic variability dose-limiting toxicity; has narrow window, there significant pharmacokinetic–pharmacodynamic relationship. Measures exposure area under time–concentration curve have been both toxicity outcomes, making management this an unmet clinical need. The current methodologies measuring DTX are based on physical methods, analysis less available costly. An automated immunoassay developed to provide greater access management. Methods: A (MyDocetaxel) using generic nanoparticle turbidimetric method can be wide variety chemistry analyzers including Beckman Coulter AU400 AU640 instruments, which were study. assay competitive format selective monoclonal antibody. Clinical Laboratory Standards Institute protocols establishing manufacturer's claims verify performance. Testing at 3 laboratories was undertaken same laboratory validation precision, accuracy, linearity. Method comparison (n = 89) done samples collected from patients therapy. comparative LC–MS/MS validated according Food Drug Administration guidance bioanalytical methods. Institutional review board approval obtained prospective collection Results: uses 2 μL sample, provides first result 9.0 minutes generate 400 determinations per hour. Internal studies established lower limit detection ≤25 ng/mL quantitation ≤30 ng/mL. Additional demonstrated no interference coadministered drugs, major metabolites, or related compounds. Linearity 50 1000 validated. comparisons between gave slopes: 1 ± 0.5, intercepts: < 2.0 ng/mL, R > 0.99, range concentrations measured by 31–9754 mean 689 In all laboratories, coefficient variation percentage repeatability ranged 0.8% 6.2% within-laboratory precision 1.4% 10.1%. Conclusions: suitable quantifying plasma advantages small sample size, pretreatment, ability applied analyzers. With method, application testing practice may gain wider acceptance individualizing patient dosing.