What biological sample is usually used for Therapeutic Drug Monitoring (TDM)?

Plasma or Serum is the Primary Biological Sample Used for Therapeutic Drug Monitoring (TDM)

Plasma or serum samples are the standard biological matrices used for therapeutic drug monitoring (TDM), not urine, tissue, bile, stool, or ascitic fluid. 1

Why Blood (Plasma/Serum) is Used for TDM

Plasma or serum is the preferred biological sample for TDM for several important reasons:

• Direct correlation with clinical effects: TDM is based on the fundamental assumption that there is a well-defined relationship between drug plasma concentration and clinical effects (therapeutic effect, adverse effects, and toxicity) 1

• Established therapeutic ranges: For many medications, therapeutic ranges have been established specifically for plasma/serum concentrations, not for other biological fluids 1

• Standardized methodology: Analytical procedures for TDM have been optimized and validated specifically for plasma or serum samples 1, 2

• Clinical accessibility: Blood collection is relatively straightforward in clinical settings compared to other biological samples 2

Technical Aspects of Plasma/Serum TDM

When performing TDM using plasma or serum:

• Analytical sensitivity requirements: Drug concentrations in plasma are typically low, often in the nmol/L (ng/mL) range, requiring highly sensitive and selective analytical methods 1

• Common analytical techniques:

  • Gas chromatography (GC) with mass spectrometry (GC-MS) or nitrogen phosphor detectors (GC-NPD)
  • High-performance liquid chromatography (HPLC) with various detectors:
    • Ultraviolet (UV) detection
    • Fluorescence detection
    • Mass spectrometry (LC-MS/MS) - increasingly the method of choice due to high selectivity and sensitivity 1, 2

• Sample preparation: Blood samples require preparation before chromatographic separation, which may include protein precipitation, liquid-liquid extraction, or solid-phase extraction 2

Alternative Biological Samples

While plasma/serum is the standard, there are emerging alternatives in specific contexts:

• Dried blood spots: Being increasingly used as a less invasive alternative to traditional blood sampling 2

• Saliva: Can be used as a non-invasive sample for certain drugs, though not as widely established as plasma/serum 2, 3

• Urine: While sometimes used for drug monitoring, it is more commonly employed for qualitative detection of drug use/abuse rather than for therapeutic monitoring of drug levels 2

Clinical Applications and Indications for TDM

TDM is particularly valuable in the following situations:

• Drugs with narrow therapeutic index
• High interindividual pharmacokinetic variability
• Suspected non-compliance
• Lack of clinical response at recommended doses
• Suspected drug interactions
• Suspected toxicity
• Special populations: Children, elderly, patients with impaired liver/kidney function 1, 4

Practical Considerations

• Cost implications: TDM for a single psychoactive drug typically costs between 20-80€, including staff, instrumentation, chemicals, and other materials 1

• Timing of sample collection: Blood should be collected at appropriate times based on the drug's pharmacokinetics, often at trough levels (just before the next dose) 1

• Interpretation: Results should be interpreted in the context of clinical judgment, with consideration of the recommended therapeutic range for the specific drug 1

In conclusion, while various biological samples can theoretically be used for drug concentration measurements, plasma or serum samples remain the gold standard for therapeutic drug monitoring in clinical practice due to established methodologies, validated therapeutic ranges, and direct correlation with clinical effects.