|
|
Abstract
Results of a pilot study on nelfinavir ONLINE®, TDM assay of HIV protease inhibitor nelfinavir
D. Burger1, T. Berg2, M. Teulen1, C. Claudius2, C. Lawrence3, G. Soriano3, B. Hosein3, I. Domke4, M. Jung4
Background: For Therapeutic drug monitoring (TDM) of protease inhibitors in HIV Therapy currently only chromatographic methods are available. The nelfinavir ONLINE TDM assay* is a fully-automated homogenous immunoassay for TDM applications on clinical analyzers. The performance of this assay was tested in a pilot study in two laboratories using Roche/Hitachi 917 and COBAS INTEGRA® 400 analyzers.
Methods: In this automated immunoassay a nelfinavir-aminodextran conjugate aggregates rapidly with nelfinavir specific antibodies coated on microparticles. This aggregation, which can be quantified by changes in absorbance of scattered light, is inhibited by nelfinavir and its equally active metabolite M8 in the sample.
Results: Intra-Assay precision using controls 0.8/3/6 mg/ml ranged from 0.8 to 5.6 % CV. Inter-Assay precision with human sample pools and controls (0.8 to 6 mg/ml) resulted in CVs of 1.8 to 5.2 %. The lower limit of quantification, defined as the lowest nelfinavir concentration tested with an inter-assay CV below 20 %, was < 0.4 mg/mL, well below the clinically relevant nelfinavir+M8 minimum effective concentration of 0.8-1.0 mg/ml. Method comparison studies of the immunoassay against HPLC and LC-MS/MS methods using clinical serum / plasma from HIV-infected patients, yielded Passing / Bablok regression lines of y = 1.03x – 0.13 (Roche/Hitachi, N=55; R=0.985), and y = 1.01x – 0.20 (COBAS INTEGRA, N=46; R= 0.975). Furthermore the results of Proficiency testing samples from an International Quality Control Program (KKGT) were in accordance with the programs certification criteria for nelfinavir.
Conclusions: The nelfinavir ONLINE TDM assay* shows good precision, high analytical sensitivity, and comparability to chromatography-based reference methods. The fully automated immunoassay offers fast turnaround time (approx. 10 min), low sample volume (3 ml), and no sample pre-treatment.
*This assay is currently in development and has not been approved for use in the US by the FDA. COBAS INTEGRA and ONLINE TDM are trademarks of Roche.
AIDS 2006 - XVI International AIDS Conference
Abstract no.
TUPE0101
Suggested Citation
"D.Burger, et al.
Results of a pilot study on nelfinavir ONLINE®, TDM assay of HIV protease inhibitor nelfinavir.
:
AIDS 2006 - XVI International AIDS Conference:
Abstract no.
TUPE0101"
|
|
|