SOFT 2004 Meeting Abstracts - Society of Forensic Toxicologists

C32
URINARY EXCRETION RATES OF KETAMINE AND NORKETAMINE FOLLOWING
THERAPEUTIC KETAMINE ADMINISTRATION: METHOD AND DETECTION WINDOW
CONSIDERATION.
Piotr Adamowicz·, Maria Kala
Institute ofForensic Research, ul. Westerplatte 9, 31-033 Krakow, Poland
Ketamine is widely used in veterinary medicine. Its medical application in humans is limited to children because
in adults it induces severe psychedelic episodes. In recent years, ketarnine has been (ab)used by teenagers as a
recreational and club drug because of its hallucinogenic or stimulant effects. Ketarnine is also (mis)used as a 'daterape'
drug - to induce amnesia in unsuspecting victims. In a typical scenario, ketarnine is surreptitiously added by
the perpetrator to the alcoholic beverage ofan unsuspecting person, who is subsequently sexually assaulted while
under the influence ofthis substance. Many victims do not report the incident until several days after the event.
This situation creates a demand for sensitive analytical methods to reveal the presence of the drug and/or
metabolites in biological specimens collected from the victim. The second very important parameter in drug
testing for forensic purposes is the detection window - how long after drug administration a person tests positive
for the drug or metabol ite.
Sensitive gas chromatography-mass spectrometry negative chemical ionization (NCI-GC-MS) and liquid
chromatography-mass spectrometry atmospheric pressure chemical ionization (APCI-LC-MS) methods for the
simultaneous quantification of ketarnine and its major metabolite - norketamine in urine were developed and
validated. These methods were used to study the elimination ofketamine and norketamine in urine collected from
six hospitalized children (age 4-13 years) who had received a single intravenous dose ofketarnine as an anesthetic
for short surgical procedures. The doses ranged from 0.75 to 1.59 mglkg. Individual urine samples were collected
every day or once every two days for 4-16 days.,~
Target analytes were isolated from urine samples after enzymatic hydrolysis (with B-glucuronidaze) followed by
solid phase extraction (HCX column). Ketamine-D 4 and norketamine-D 4 were used as internal standards. For
NCI-GC-MS procedure, extracts were derivatized with HFBA. The monitored negative ions for ketamine
derivative were (mlz) 226 and 357, for norketarnine, 383 and 399, and for norketamine-D 4 , 387 and 403. APCI­
LC-MS analyses were carried out without analytes derivatization. Pseudomolecular ions of (mlz) 224 and 228
(for norketarnine-Do and -D 4 ), 238 and 242 (for ketamine-Doand -D4) were monitored.
The NCI-GC-MS assay had an LOQ of 20 nglmL for ketamine and of 50 pg/mL for norketamine, and
displayed LOL across a concentration range of 20-1000 nglmL and 50-I 500 pg/mL for parent drug and
metabolite respectively. LOQ and LOL for the APCI-LC-MS method were 2 nglml and 2-2000 ng/mL for
both compounds. For the NCI-GC-MS, mean inter-day precision for ketamine and norketamine ranged
from 21.4-30.4% and 16.8-23.6%, respectively. For the APCI-LC-MS, mean inter-day precision for both
compounds were between 1.6-3.7%.
Using NCI-GC-MS, ketamine was detected in urine of four persons up to 1 day and in one up to 2 days
after drug administration. Its concentrations ranged from 58 to 1181 ngimL. Norketamine (measured in
concentrations of 1.18 !J.glmL-50 pglmL) was detected up to 14 days (average 7 days). Using the APCI­
LC-MS method, ketamine was detected in two persons up to 2 days, in one up to 4 days, in one up to 11
days and in one only up to one day at concentrations of 2-813 ngimL. Norketamine (at concentrations of
1276-2 nglmL) was detected up to 3, 4, 5 and 6 days after drug administration. In one person, ketamine
was not detected through the entire 16-day period using both methods.
Detection window of the analytes is highly dependent on the method used for determination and
interindividual variability.
Keywords: ketamine, norketamine, detection window, drug facilitated sexual assault
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