Pharmikos Pharmacology Consulting                                    John Lehmann PhD Scientific analysis of therapeutic and side effects of drugs, data interpretation, causation, patent claims, NDAs
 

Drugs tests on blood or urine can be screens using immunoassay or quantitative GCMS. Pharmacokinetics / Toxicokinetics aids accurate interpretation. Eia / Elisa are immunoassays

 

 

 

 

 

 

 

Pharmikos > Focus Areas > Drug Metabolism and Blood Levels

Pharmacokinetics. The change in the distribution and chemical properties of a drug after administration to a human or animal is termed pharmacokinetics. Pharmacodynamics refers to the time course of effects of the drug after administration. There is unfortunately a considerable lack of correlation between these two measures. The effects of drugs often subside long before drug levels have diminished. Both Pharmacokinetics and Pharmacodynamics give unique and essential insight into drug mechanisms.

Data Sources - Analytical Chemistry. Scientists among scientists devote considerable attention to the methods used to obtain data, and scrutinize the data before drawing conclusions. In contrast, forensic laboratories, the courts, and the legal community in general seems to have little patience and expertise for examining these aspects, but readily accepts data as valid, racing off to various interpretations.

Blood levels of Drugs. Blood samples are obtained from living persons or post-mortem. Some drugs are susceptible to Drug Redistribution as part of the post-mortem process. Serum Drug Levels may be significantly different from Plasma Drug Levels, altering interpretation. Some drugs are highly bound to proteins in blood.

Urine levels of Drugs. Urine has more shortcomings than blood levels for technical reasons and also interpretive reasons. Whereas blood levels are always changing and often reflect the bioactive concentration of drug, urine levels (of the drug or its metabolite) give a retrospective estimate of the amount of drug elimination since last bladder voiding. The volume of urine is a relevant parameter also which affects the detected drug concentration, and is affected by the hydration state of the subject. For these reasons, drug tests performed on urine are typically non-quantitative, and only intended to give an indication whether a drug has or has not been used "recently".

 

After blood or urine samples are taken to the laboratory (or field tested), the instrumentation and methods used to analyze them are crucial. Primarily two methods will be discussed here: Immunoassy and Gcms.

Immunoassay (Elisa, Eia, Enzyme-Linked ImmunoSorbent Assay). Immunoassay is the typical front-line test for urine, particularly at hospitals or police stations. A single immunoassay test should never be relied upon to draw important conclusions. This opinion is not only embraced in scientific and medical circles, but has been a part of the federal policy concerning occupational drug testing. For some drug tests, there are interfering substances possible that can give false positive or false negative results. The sole purpose of performing an immunoassay is to "screen" samples for possible submission for testing by more reliable methods.

GCMS (Gas Chromatography / Mass Spectroscopy; Gcms). The most commonly used highly reliable method for identifying drugs or metabolites is GCMS. This is actually two analytical methods combined into one. The gas chromatograph first separates the analytes based on chemical properties. The output from the gas chromatograph is fed directly to a mass spectrometer. Analytes can then be identified according to their physical properties (mass) and characteristic fragmentation. Furthermore, GCMS can and should make use of internal, deuterated standards, which serve as premium internal controls for the handling of the sample from the point that the internal standard is added. But good instrumentation does not necessarily result in reliable data. Many errors by the operator are possible. Quantitative discrepancies between GCMS laboratories are common.

Retention of samples. The scientific criterion for reliability of a result is replicability; if possible, one never relies on a single assay result, as mistakes can occur. Samples should be retained such that two independent laboratory determinations can be made.

Food and Drug Administration Fda Center for Drug Evaluation and Research Cder National Institutes of Health Institute of Medicine, National Academy of Sciences: To Err is Human
Caltech, the California Institute of Technology The Johns Hopkins University School of Medicine Novartis Pharmaceuticals, formed by the merger of Ciba-Geigy and Sandoz
 
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