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Journal of Analytical Toxicology, Vol. 32, March 2008
Letter to the Editor
I
Elimination Half-Lives of Benzoylecgonine
and MDMA in an Apprehended Driver
To the Editor:
After a zero-tolerance law was introduced in Sweden for driving under the influence of drugs (DUD), the number of blood
samples sent by the police for toxicologicalanalysis increased more than 10-fold (1). Central stimulant amines, as exemplified by
amphetamine and methamphetamine are highly prominent in DUD suspects and are identified in 50-60% of all cases (2). Other
stimulants encountered in blood from impaired drivers, although much less frequently, are cocaine and ecstasy (MDMA)(2).
This report concerns a 27-year-old man apprehended by the police on suspicion of impaired driving on three separate
occasions during a 24-h period. Blood samples for forensic analysis were obtained with the aid of evacuated tubes containing
100 mg sodium fluoride and 25 mg potassium oxalate as preservatives. The times of sampling blood were 2:03 p.m., 10:27 p.m.,
and 3:30 a.m. the next day. Table I gives the sampling times and the concentrations of benzoylecgonine (BZE), amphetamine,
MDMA, and MDA in the blood samples.
After an initial screening analysis of blood by immunoassay methods all positive results were verified by more specific
methods involving gas chromatography-mass spectrometry (GC-MS) and deuterium-labeled internal standards. The limit of
quantitation (LOQ) for amphetamine in blood was 30 ng/mL, compared with 20 ng/mL for MDAand MDMA.The corresponding
LOQ for cocaine and BZE in blood analyzed by GC-MS was 20 ng/mL.
The concentrations of BZE and MDMAat the three sampling times were used to calculate the elimination rate constants for
these substances, assuming first-order kinetics, by fitting a least-squares regression equation of the form:
In (Ct) = In (Co) - k~ t
In this equation, Ct is drug-concentration at time t, Co is the y-intercept, and ke is the first order elimination rate constant.
The elimination half-life (t~) is calculated from the following relationship:
t~ = In 2/ke = 0.693/ke
The values of t~, derived mathematically
and reported in Table I, agreed well with
graphical estimates obtained using a
semi-logarithm plot and extrapolation.
A search of the scientific literature showed
that the elimination half-life of BZE is much
longer than that of the parent drug cocaine
(3,4). In the present traffic case, BZE was
measurable over a 1389 period when the
concentrations of cocaine in blood were
below LOQ (20 ng/mL) at all three sampling
times (Table I). The elimination half-life of
cocaine shows large individual variations
depending on dose and route of
administration, whether intravenous,
intranasal, or by smoking (3-5). The half-life
of BZE in this DUD case was 6.4 h, which
agrees well with information from controlled
dosing studies (3-5).
Amphetamine has a long elimination halflife (7-34 h), and the drug might be
measurable in plasma and urine for several
Table I. Concentrations of Drugs in Three Successive Blood Samples from
an Apprehended Driver
Drug Presentin
Blood Sample
Benzoylecgonine*
Sampling Concentration
Time
(ng/mL)
2:03 p.m.
10:27 p.m.
389
135
3:30 a.m.
95
In C t = In C0 - ket
t,h = In 2/ke
In C, = 5.94 - 0.109 t
r2 = 0.978*
6.4 h
Amphetamine
2:03 p.m.
10:27 p.m.
03:30 a.m.
440
421
525
Not applicable
Not
applicable
MDMA
2:03 p.m.
10:27 p.m.
03:30 a.m.
219
137
87
In Ct = 5.42 - 0.0673 t
r2 = 0.983 t
10.3 h
MDA*
2:03 p.m.
I0:27 p.m.
03:30 a.m.
Not applicable
Not
applicable
20
15w
11w
* Concentrationof cocaine below LOQ (20 nglmL) at each sampling time,
r2 = coefficient of determination.
* Metabolite of MDMA.
wBelow LOQ (20 ng/mL).
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1 97
Journal of Analytical Toxicology, Vol. 32, March 2008
days after abuse-level doses (6). The plasma half-life depends to some extent on urinary pH, with alkaline urine leading to
retention in the blood (t~ = 18-34 h) and acidic urine promoting renal clearance and resulting in a shorter plasma half-life of
7-14 h (6). Table I indicates that the concentration of amphetamine in blood increased slightly between the time of obtaining
the second and third samples. This suggests that the DUID suspect might have taken a fresh dose of the drug, which precludes
calculating an elimination half-life for amphetamine.
The half-life of MDMAin this individual was 10.3 h (Table I), which agrees well with results from a few controlled dosing
studies with this designer drug (mean t~ 9 h, standard deviation 2.3, n = 8) (7-10). The concentrations of MDMA'smetabolite
MDAwere below LOQ in all but the first blood sample, which precludes estimating the elimination half-life of MDA.
Human pharmacokinetic studies with illicit drugs are not feasible to undertake in most countries because of ethical
constraints as well as various legal restrictions. Such studies are usually done at hospital or prison environments with strict
control of all participants and administration of a single moderate dose of the drug. Moreover, drugs and their metabolites are
usually analyzed in plasma or serum and not in whole blood, which is the biological matrix available for forensic toxicology
(1,2,11). The Cmaxafter dosing, the elimination half-life and the volume of distribution might also depend on the dose of drug,
the route of administration and the biological matrix analyzed (11).
Caution is warranted whenever half-lives of illicit drugs are cited in forensic casework because the number of human dosing
studies are relatively few and participants are limited (usually n = 6 to 8). In some publications it is not always made perfectly
clear whether t~ was derived from concentration-time plots for individual subjects or from an average curve for all subjects. The
biological matrix analyzed, whether plasma, serum, or whole blood can impact on the elimination half-life as well as other
pharmacokinetics parameters (11).
The pharmacokinetics of a drug after therapeutic doses is not necessarily the same as after abuse doses because of enzyme
induction and metabolic tolerance, which is often the situation in forensic toxicology casework. Instead of citing a definitive
half-life for a particular drug, it would be more prudent to give a range of values or simply classify drugs as having short halflives (e.g., GHB, 6-acetylmorphine, and cocaine), intermediate half-lives (e.g., morphine, codeine, and ethyl morphine), or long
half-lives (e.g., diazepam, methamphetamine, and methadone).
Three successive blood samples are not ideal for a pharmacokinetic evaluation and the calculation of an elimination half-life.
However, opportunities to perform such calculations in actual cases of impaired driving are rare, which motivates this short
communication. The half-lives found for BZE (6.4 h) and MDMA(10.3 h) in this impaired driver are consistent with those
published in the scientific literature.
A.W. Jones
Department of Forensic
Genetics and Forensic Chemistry,
National Board of Forensic Medicine,
Artillerigatan 12, SE-581 33
Link6ping, Sweden
References
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drivers in Sweden. Traffic Inj. Prey. 8:361-367 (2007).
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870-880 (1973).
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9. R. de la Torre, M. Farr~, J. Ortuffo, M. Mas, R. Brenneisen, P.N. Roset, J. Segura, and J. Carol. Non-linear pharmacokinetics of MDMA ("ecstasy") in humans. Br. J. Clin. Pharrnacol. 49:104-109 (2000).
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