Understanding “cut-offs” in drug testing

Why a result may be reported as “Not detected” even though the individual has taken some drugs

When testing drugs in urine, saliva or hair samples, results are evaluated against “cut-offs” for each of these type of samples for interpretation before the issue of certificate of analysis.

“Cut-off” is a value which the results obtained in the analysis are compared against. When results are below the cutoff, they are considered as “Not Detected “or” Negative “, and when  above they are considered” Detected “or” Positive “

Cut-offs may vary between different analytes

The cut-off for cocaine in hair samples is 0.5 nanograms per milligram (ng/mg) of hair and the cut-off for the metabolite of THC (which is the main component of cannabis), the 11-Nor-D9-THC-9-Carboxylic Acid (THC COOH) is 0.002 ng/mg of hair.

This remarkable difference between the cut-off levels of cocaine and THC COOH in hair  is due to the different rates of incorporation of these compounds into the hair sample [1].

Cut-offs may change according to type of sample analysed

Each drug or metabolite has its own cut-off according to the type of sample tested, i.e., whether urine, oral fluid or hair samples are used in the analysis. For example, the cut-off for cocaine in urine is 300 nanograms per millilitre (ng/mL) of urine and in hair is 0.5 ng/mg of hair, when analysed by LC-MS/MS.

The cut-off values of different types of sample, usually reflect the levels of drugs that are found in them. For example, levels of cocaine in a survey of over 7,000 hair samples were over a range from 0.2 to 159.9 ng/mg of hair in 99% of the samples [2]. In the same study, 99% of the levels found in the results of the metabolite of THC  the THC COOH, were in the range from 0.001 to 0.052 ng/mg of hair.

In the case of urine and  oral fluid, the levels of cut-offs are used:

a) to reduce the chance of reporting that drugs have been taken when the drugs were taken involuntarily (passively), as is the case with drugs that are smoked;

b) to eliminate the detection of drugs, when drugs were used at an earlier time (for example, eliminating the detection of drugs used over the weekend outside the workplace). This is very important in the workplace, where it is crucial to know whether an individual is under the influence of drugs or not, so as to minimise risk of injury to colleagues and the general public.

In practice, it means that results of urinalysis are reported as “Not detected” when levels are below the established cut-off even though the presence of drugs is clear.

A positive result of an urine or oral fluid analysis may be used to confirm if a person has used or was exposed to a drug. A negative result, however, does not refute use of or exposure to the drug

In contrast with the cut-offs employed in urinalysis, the cut-offs for hair samples are much lower and are usually at around the limit of the detection of the methods (all methods have a minimum levels below which they cannot detect drugs). This is in contrast with the cut-offs employed in urinalysis, which are much higher than the limitation of the methods, which means that results of urinalysis are reported as “Not detected”even though the presence of drugs is clear.

The cut-offs employed in hair analysis are usually analytical cut-offs established at the limit of quantification of the methods used

The main purpose of the cut-offs used in drug hair analysis are:

a) to minimise detection of drugs used in previous periods and increase detection of current use;

b) to minimise the detection of drugs deposited from external contamination  when the people tested don’t use drugs but they are in an environment where drugs are being handled.

This explains why the cut-off for cocaine is currently 0.5 ng/mg (and not 0.2 ng/mg or less) when current use is to be detected, not past use, and also to minimise external contamination in the case of cocaine [3].

Cut-offs vary depending of the method of analysis

Cut-offs vary according to the methodology used, thus, cut-offs for screening tests by immunoassays are usually different from those analysed by chromatographic methods. For example, according to SoHT guidelines for drug hair testing, when testing for cannabis use, the cut-off test for THC using an immunochemical is 0.1 ng/mg and for a chromatographic test the metabolite THC-COOH is 0.002 ng/mg of hair.

Cut-offs may vary between testing laboratories

Testing laboratories utilise different procedures in the analysis of the samples in conjunction with different equipment. These and the experience of the testing laboratory will have an impact in the the cut-offs levels and results. It is therefore important that before performing the analysis, clients are informed of the uncertainty of the measurement at the cut-off levels.

Uncertainty of measurement at Cut-off

The total uncertainty of a result of a  hair test is derived mainly from the pre-analytical and analytical variations that contribute to the total uncertainty of drug detection in hair [4]. The uncertainties of biological measurements should be considered when interpreting the resulting data.

The uncertainties associated with the measurements and with the interpretations and any assumptions made during the process should be explicitly stated to the clients by the testing laboratory

[1] Nakahara, Y, Takahashi, K, Kikura, R. (1995) Hair analysis for drugs of abuse, X: effect of physicochemical properties of drugs on the incorporation rates into hair. Biol.Pharm. Bull. 18, 1223.

[2] Tsanaclis, L, Wicks, JFC. (2007) Patterns in drug use in the United Kingdom as revealed through analysis of hair in a large population sample. Forensic Sci. Int. 170 (2-3): 121-128.

[3] Tsanaclis, L, Nutt, J, Bagley, K, Bevan, S, and Wicks, J (2014). Differentiation between consumption and external contamination when testing for cocaine and cannabis in hair samples. Drug Testing and Analysis 6, 37-41.

[4]  Nielsen, MKK., Johansen, SS, Linnet, K. (2014) Pre-analytical and analytical variation of drug determination in segmented hair using ultra-performance liquid chromatography–tandem mass spectrometry. Forensic Sci. Int. 234, 16-21. 

 

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