Drug Analysis and Toxicology Method Validation

Absorption

Penetration of a substance into an organism by various processes eg carrier system, passive diffusion.

Systemic Absorption

Uptake into the blood and transport via blood to an organ or compartment of the body distant from the point of entry.

Absorbed dose

Amount taken up by organism into organs or tissues of interest.

Active metabolite

Metabolite with pharmacological or toxic activity.

Metabolism

Sum total of all physical and chemical processes that take place within an organism.

Intentional poisoning

Murder or attempted murder.

Administration of noxious substances

Assist Coroner to ascertain cause of death.

Suicide

Self-inflicted death.

Accidental poisoning

Unintentional ingestion or exposure to harmful substances.

Driving under influence

Operating a vehicle while impaired by drugs or alcohol.

DFSA

Drug-Facilitated Sexual Assault.

Adulterations

The act of making something poorer in quality by adding another substance.

Drug Testing

The analysis of biological samples to detect the presence of drugs.

Tissue Selection

Selection of tissue depends on the type of poison and subject circumstances (living or dead).

Blood pm

Post-mortem blood sample.

Urine?

Sample that can be collected easily but mainly contains inactive drug metabolites.

Hair

Non-invasive sample that provides a long time window for drug history.

Liver

Reflects what is circulating in the body and can comment on the likelihood of producing an effect.

Vitreous humour

Sample from deceased only; interpretation limited but protected from microorganisms.

Breast milk

Determines neonate exposure but is invasive to collect.

Gastric content

Good for screening, indicating recent ingestion or delayed gastric emptying.

Verification

Evaluation experiments conducted to determine whether certain specifications are met.

Demonstration

Evaluation studies conducted by a laboratory to show that it can obtain expected performance.

Evaluation

A generic name for any study that measures the performance capabilities of an assay.

Validation

Evaluation experiments conducted to determine whether a test system meets laboratory requirements.

Allowable Error (EA)

The amount of error that can be tolerated without invalidating the medical usefulness of the result.

Decision Limit (Xc)

Any concentration of analyte that is critical for medical interpretation.

Testing Personnel

Individuals trained in equipment and procedures.

Validation Plan

Document outlining required materials and procedures.

Performance Standards

Criteria for acceptable results in testing.

Experimental Protocols

Detailed procedures for reliable performance estimation.

Interference

Non-target analytes affecting detection or quantitation.

Precision

Reproducibility of results expressed as SD or CV%.

Linearity

Proportionality between test results and analyte concentration.

Accuracy

Closeness of a measured value to the true value.

LOQ

Lowest detectable analyte amount meeting accuracy requirements.

Ion Suppression

Reduced ionization due to co-eluting compounds.

Ion Enhancement

Increased ionization caused by co-eluting compounds.

Recovery

Comparison of detector response from added analyte.

Recovery Calculation

Formula to determine recovery percentage of analyte.

Calibration Model

Procedure for establishing analyte concentration standards.

Carryover

Unintended analyte signal in subsequent samples.

Carryover Criteria

Factors affecting carryover in analytical methods.

Post Validation

Summary of validation studies and results.

Method Validation Record

Documentation of validation studies and results.

Sample Preparation Steps

Procedures including concentrations and matrices used.

Management Review

Documentation of approval for validation processes.

Common Sample Abnormalities

Conditions like hemolysis affecting test results.

Contaminants

Substances introduced during sample handling.

Specificity Issues

Challenges in distinguishing analytes in methods.

Example 1

Cocaine assay must assess interference from drugs.

Example 2

Ethanol assay must evaluate volatile compound interference.

Optimum Recovery

Ideal recovery percentage is 100%.

Calibration Samples

Prepared at specified concentrations for validation.

R2 Criteria

Correlation coefficient should exceed 0.975.