title: Development and evaluation of a nanoparticle-based immunoassay for determining paclitaxel concentrations on routine clinical analyzers.
abstract: BACKGROUND
  Paclitaxel (PTX; Taxol, Abraxane) is used in many regimens for breast cancer, non-small cell lung cancer (NSCLC), and ovarian cancer. Multiple studies have demonstrated that PTX exhibits a greater than 10-fold interpatient variability of clearance rates when patients are dosed according to body surface area (BSA). Pharmacokinetic and pharmacodynamic relationships have been elucidated from BSA-based dosing. PTX is a candidate for dose management, and studies have shown that therapeutic dose management (TDM) is feasible and may provide improved outcomes for patients undergoing treatment.
  
  
  METHODS
  A PTX immunoassay (MyPaclitaxel) has been developed, which employs a novel PTX monoclonal antibody in a nanoparticle-based turbidimetric assay in a competitive format. Precision, accuracy, and linearity were evaluated by Clinical Laboratory Standards Institute protocols at 3 laboratories on the Olympus AU400 analyzer. Method comparison was done versus a validated high-performance liquid chromatography-tandem mass spectroscopy method using samples (n = 119) collected from patients on PTX therapy.
  
  
  RESULTS
  The assay requires 8 μL of plasma sample and can produce 400 determinations per hour. The response curve is based on a 6-point nonlinear curve fit and has a range of 0-320 ng/mL, extended to 3200 ng/mL with 10-fold autodilution. Three controls and 4 patient pools were used in precision studies. For all samples across 3 sites, repeatability coefficient of variation percentages ranged 0.9%-4.9%, and within-laboratory coefficient of variation percentages were 1.0%-4.2% with standard curve stability up to 24 days. Linearity was demonstrated over the linear range. Lower limits of detection and quantitation were 11 and 19 ng/mL, respectively. Method comparison results were analyzed by Deming regression, demonstrating a slope = 1.002 and intercept = -3.029 and an R = 0.996. The PTX samples ranged from 24 to 3164 ng/mL with a mean of 745 ng/mL.
  
  
  CONCLUSIONS
  The analytical performance of an automated immunoassay for PTX has been validated and may serve as a useful tool for TDM of this drug.
authors.affiliation: *Saladax Biomedical, Inc, Bethlehem, Pennsylvania; and †FALCO biosystems Ltd, Nakagyo-ku, Kyoto, Japan.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cline
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhang
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Lundell
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Harney
authors.forename: Hadia K
authors.initials: HK
authors.lastname: Riaz
authors.forename: Justin
authors.initials: J
authors.lastname: Jarrah
authors.forename: Yunying
authors.initials: Y
authors.lastname: Li
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Jodi B
authors.initials: JB
authors.lastname: Courtney
authors.forename: Irina
authors.initials: I
authors.lastname: Baburina
authors.forename: Salvatore J
authors.initials: SJ
authors.lastname: Salamone
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000097:blood*; D001331:Automation; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D057230:Limit of Detection; D053758:Nanoparticles; D017239:Paclitaxel / Q000097:blood*; D011446:Prospective Studies; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel