Abbott TDX

Reference interval

• see specific procedure for reference values listed for each analyte

Principle

The TDx System is a completely automated system used for the quantitation of therapeutic drug concentrations & clinical chemistries in serum & plasma, as well as toxic/abused drugs in serum & urine. The TDx System consists of an automated analyzer, assay kits, standards, & controls for various drugs. The system is primarily designed to measure drug levels of anticonvulsant, antibiotic, antiasthmatic, & cardiovascular Drugs.

The field of therapeutic drug monitoring brings together many disciplines including drug analysis, drug metabolism, pharmacokinetics, & toxicology. If a prescribed drug is to be therapeutically effective, it must be present at its receptor site in sufficient concentration. Attainment of therapeutic drug receptor saturation requires the administration of the appropriate amount of drug at the proper time intervals. Since drug receptor site assays are not available, blood level monitoring is used as a guide to the therapeutic efficacy of the chosen dosage schedule. The blood levels are affected by the pharmacokinetic processes of absorption, distribution, metabolism & excretion which are different in each patient. Therefore, the same dose of a drug may produce large differences between individuals in the serum concentration of the drug. Drug level monitoring allows precise adjustment of a patient's dosage & schedule to each person's individual therapeutic requirements, thereby maximizing efficacy while minimizing unwanted side effects.

The TDx System has become the standard for monitoring therapeutic drug & hormone levels using fluorescence polarization immunoassay (FPIA) technology & competitive binding immunoassay methodology.

The tungsten halogen lamp in the system emits light of different wavelengths or colors with random spatial orientation. An interference filter, located in front of the light source, allows only blue light (481-489 nm) to pass through. The light then passes through a liquid-crystal polarizer to produce a single plane of polarized blue light. The plane of polarized blue light excites the tracer, or fluorophore, & raises it to an excited state. After excitation, the fluorophore returns to steady state by emitting green light (525-550 nm). When the fluorophore is bound to a large antibody molecule, it rotates slowly, & the emitted green light is in the same plane as the blue excitation light; polarization is retained. Conversely, when the fluorophore is free it rotates rapidly, & the emitted green light is in a different plane than the blue excitation light; polarization is lost. Because of the rotational properties of molecules in solution, the degree of polarization is directly proportional to the size of the molecule. Polarization increases as molecular size increases.

The TDx System uses a competitive binding immunoassay methodology to allow tracer-labeled antigen & patient antigen to compete for binding sites on the antibody molecules. The components in this competitive binding reaction are the antibody, the patient antigen, & the antigen labeled with fluorescein (tracer-antigen complex). When competitive binding occurs, the more tracer- antigen complex that binds to the antibody molecule, the less tracer-antigen complex that remains in solution. If a patient sample contains a low concentration of antigen, after the competitive binding reaction reaches steady-state, there is a high concentration of bound tracer in the reaction mixture & polarization is high. Conversely, if a patient sample contains a high concentration of antigen, after the competitive binding reaction reaches steady-state, there is a low concentration of bound tracer in the reaction mixture & polarization is low.

The precise relationship between polarization & concentration of the unlabeled drug or hormone in the sample is established by measuring the polarization values of calibrators with known concentrations of the drug or hormone.

Using the polarization values generated for each sample in the assay, concentrations of drugs or hormones in unknown samples are calculated using the stored calibration curve, & the results are printed out in reportable units.

Clinical significance

• see discussion for each individual analyte for specific information

Specimen

Collect blood samples by venipuncture following established good laboratory practices. If the sample is obtained through the infusion set, flush the line thoroughly with saline before taking the blood sample. With some exceptions, any anticoagulant may be used to collect plasma for analysis. Serum, as well as plasma, may be used for most assays. It is very important that the physician be informed of the times of sample collection & dose administration; this information should be supplied to the laboratory with each sample & reported with the results of each test.

Samples derived from blood should be refrigerated upon collection & stored frozen (-20 degrees Celsius or colder) if not analyzed within 24 hours. Complete mixing of each thawed sample is required before analysis.

Urine samples must be collected in clean, previously unused containers. It is recommended that samples should be refrigerated upon collection & stored frozen if not analyzed within 48 hours.

CSF & amniotic fluid samples should be obtained using standard collection procedures.

Fibrin threads or large particles which could block the probe should no be pipetted or poured into the sample well. After sample transfer, assure there are no bubbles or foam present in the sample well. Remove bubbles or foam prior to running. Fluorescein is a constituent of all FPIA reagent systems. Patient samples containing fluorescent compounds may interfere with these TDx methodologies result in high blank intensity readings & low net intensities. If patient samples cannot be diluted below the maximum background value an alternate methodology should be used.

Automatic serum blank readings reduce optical interferences from grossly icteric, hemolyzed or lipemic samples. Serum blanks are automatically subtracted by the TDx analyzer before final results are printed, when required by the specific assay mode.

More general terms

• analyzer