Procedures

This section covers the various facets of laboratory test procedures in TDM

General Principles of TDM Laboratory Test Procedures

Purpose: To accurately measure drug concentrations in biological samples to optimize therapy and minimize toxicity
Analytical Methods
- Immunoassays: Based on antibody-antigen binding
- Chromatography: Separates and quantifies drugs based on their properties
Sample Types
- Serum, plasma, whole blood (depending on the drug)
Reporting Units
- ng/mL, μg/mL, mg/L, etc

Principle
- Utilizes specific antibodies to bind to the drug being measured
- The antibody-drug complex is then detected and quantified
Types
- Competitive Immunoassays: Drug in sample competes with labeled drug
- Non-Competitive Immunoassays: Antibody binds directly to the drug
- Homogeneous Immunoassays: No separation steps
- Heterogeneous Immunoassays: Require separation steps
Examples
- Enzyme-Multiplied Immunoassay Technique (EMIT)
- Fluorescence Polarization Immunoassay (FPIA)
- Chemiluminescent Microparticle Immunoassay (CMIA)
Advantages: High throughput, ease of use, and automation
Limitations: Potential for cross-reactivity, matrix effects, and interference from heterophile antibodies

Principle
- Separates drugs and metabolites based on physical and chemical properties
- Quantifies the separated compounds using various detectors
Types
- High-Performance Liquid Chromatography (HPLC)
- Liquid Chromatography-Mass Spectrometry (LC-MS/MS)
- Gas Chromatography (GC)
Detectors
- UV-Vis, fluorescence, mass spectrometry
Advantages: High specificity and sensitivity, ability to measure multiple drugs/metabolites simultaneously
Limitations: More complex, requires skilled operators, and more expensive than immunoassays

Patient Preparation
- Timing of dose: Collect samples at appropriate times (trough, peak)
- Medication history: Document all medications and supplements
- Fasting requirements: May be needed for some tests
Sample Collection
- Use correct collection tubes
- Follow the correct order of draw
- Proper venipuncture technique to minimize hemolysis
- Label specimens immediately and accurately
Sample Handling
- Process promptly
- Aliquot correctly
- Store at correct temperature
- Protect from light if necessary

Specimen Types: Serum, plasma, whole blood
Collection Tubes: SST, EDTA, heparin
Centrifugation: Centrifuge promptly after collection
Separation: Separate serum or plasma from cells within the specified time frame
Storage: Refrigerate or freeze samples at recommended temperatures

High Drug Results
- Pre-analytical: Wrong collection time, medication administration error, contamination
- Analytical: Incorrect calibration, reagent issues, interferences
Low Drug Results
- Pre-analytical: Wrong collection time, degradation, improper storage
- Analytical: Calibration issues, reagent problems, interferences
Inconsistent Results
- Pre-analytical: Patient variability, handling errors
- Analytical: Assay variability, interferences
Quality Control (QC) Failures
- Pre-analytical: QC improperly stored or expired
- Analytical: Calibration errors, reagent issues, instrument malfunction
- Investigate and correct the source of the error