Nicotine in Blood, Serum/Plasma, Urine, Sweat, Saliva, Breast Milk, Hair, and Postmortem Tissues

AuthorJames G. Wigmore
Pages121-146

 3
Nicotine in Blood, Serum/Plasma, Urine,
Sweat, Saliva, Breast Milk, Hair, and
Postmortem Tissues
“Determination of nicotine and metabolite concentrations in biological
f‌luids at low LOQs is of increasing interest in nicotine cessation and clin-
ical investigations. Highly sensitive assays are required to detect environ-
mental tobacco exposure and to extend the window of drug detection in
nicotine cessation programs. Full analytical method validation is required
for reliable and accurate drug quantif‌ication.
—Skhakleyz and Huestis, “Optimization and Validation of a Liquid
Chromatography-Tandem Mass Spectrometry Method for the
Simultaneous Quantif‌ication of Nicotine, Cotinine, and Trans-’-
Hydroxycotinine and Norcotinine in Human Oral Fluid” ()
Nicotine and its main metabolite, cotinine, distribute throughout the
entire body and so may be detected in blood, serum, urine, oral f‌luids,
and hair. The detection times are of longer duration in hair >urine >oral
f‌luids >blood (serum).
. METHODS OF ANALYSIS
“Of the dif‌ferent body f‌luids, saliva is the matrix of choice for assessing
the presence of nicotine and its metabolites in humans exposed to ETS.
—Dhar, “Measuring Tobacco Smoke Exposure: Quantifying Nicotine/
Cotinine Concentration in Biological Samples by Colorimetry,
Chromatography and Immunoassay Methods” ()
 | Wigmore on Nicotine and Its Drug Delivery Systems
Reference Number: 
There are numerous methods to determine the concentration of nicotine
and its major metabolite, cotinine, in various biological f‌luids. The meth-
ods range from simple enzymatic tests in the urine or saliva to sophis-
ticated LC/MS/MS methods in blood or plasma (–). A sensitive
method was developed to measure nicotine in bronchoalveolar f‌luid from
EVALI (e-cigarette or vaping product associated lung injury) patients to
determine recent use of an inhalational nicotine product ().
Reference Number: 
, -., . , . , .. , .. , . ,
. , . , . , .. , . ,
.,  .. . “Nicotine Metabolite Ratio (-hydroxy-
continine/cotinine) in Plasma and Urine by Dif‌ferent Analytical Meth-
ods and Laboratories: Implications for Clinical Implementation.Cancer
Epidemiology, Biomarkers & Prevention, : –,  ( tables,
f‌igure,  references)
Abstract: Thirty-f‌ive plasma and  urine samples were spiked with nico-
tine and trans ’-hydroxycotinine (-HC) and were sent to eight dif‌fer-
ent laboratories for analysis. The labs all employed LC/MS/MS, GC/MS,
or high-performance liquid chromatography with ultraviolet detection
(urine only) methods to determine the -HC and cotinine concentrations.
The results showed better agreement in plasma than urine.
We found that plasma NMR measurements are in good agreement and
strongly correlated between methods and sites. Our results provide greater
conf‌idence that plasma NMR measures, regardless of method used here,
are consistent. These f‌indings reduce the need for dif‌ferential interpreta-
tion of plasma NMR results based on approach used to conduct the analysis.
Reference Number: 
, .., .. , . , .. , .. ,
. , .. ,  ..  . “Test-Retest Reliability and
Stability of the Nicotine Metabolite Ratio Among Treatment-Seeking
Smokers.Nicotine and Tobacco Research, : –,  (f‌igure,
 table)
Abstract: The nicotine metabolite ratio (NMR) is the ratio of -HC to
cotinine and is an indicator of slow versus fast metabolizers of nicotine.

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