12.15: Therapeutic Drug Monitoring: Drug Analysis Methods

Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood or body tissues to tailor drug therapy effectively. This monitoring is critical for managing drugs with narrow therapeutic indices like digoxin and phenytoin, ensuring they are both safe and effective. For instance, monitoring theophylline levels in asthma patients involves precision and sensitivity to adjust doses according to individual responses to therapy, ensuring efficacy and preventing toxicity.

Drug analysis methods in TDM involve the following techniques:

• Stability Testing: This ensures that drug concentrations remain stable during storage and handling, which is crucial for maintaining consistent dosing.
• Bioavailability Studies: This helps assess how drugs are absorbed and become available at the site of action, influencing dosing schedules.
• Sensitivity Assessments: Determine the minimum detectable level of a drug, which is essential for setting the lower limit of drug monitoring.
• Precision and Accuracy: These are essential qualities in TDM tests. They ensure drug levels are consistently and correctly measured, reflecting true patient exposure.
• Dynamic Range and Linearity: This evaluates how drug concentrations respond to incremental doses, helping to understand whether changes in dosage will lead to expected changes in blood levels.
• Analytical Methods: Drug analyses are typically conducted in clinical chemistry or pharmacokinetics laboratories using techniques like high-pressure liquid chromatography with mass spectrometry (LC–MS) and immunoassays. The choice of method depends on the drug's physicochemical properties, desired concentration levels, the biological specimen type, and the laboratory's available resources and expertise.
• Quality Assurance: Laboratories must adhere to standard operating procedures (SOP) and good laboratory practices (GLP), ensuring the assays' specificity, linearity, sensitivity, precision, accuracy, stability, and ruggedness are validated for timely and reliable therapeutic decision-making.

Therapeutic drug monitoring or TDM analyzes drug levels in a patient’s body to optimize therapy. For example, it helps monitor theophylline levels in asthma patients.

TDM requires precise dose adjustments based on individual responses to enhance efficacy and prevent toxicity.

Analytical methods, including LC–MS, colorimetry, spectrophotometry and immunoassays, are selected based on drug properties and laboratory capabilities.

Precision and accuracy are essential to ensure that measured drug levels reliably reflect patient exposure, supporting effective therapeutic drug monitoring.

Sensitivity assessments define the minimum detectable drug level, establishing the lower monitoring limit.

Dynamic range and linearity assessments evaluate an instrument’s response to varying drug concentrations, ensuring accurate quantification.

Stability testing confirms that drug concentrations remain unchanged during storage and handling.

While not part of therapeutic drug monitoring, bioavailability studies assess drug absorption and systemic availability to guide appropriate dosing schedules.