FORENSIC TOXICOLOGY - Bio Medical Forensics

As seen in the above data, there has been a dramatic increase in the
number of cocaine positive cases containing diltiazem in the past year.
The Drug Enforcement Administration first reported cocaine seizures
adulterated with diltiazem in 2004. 1 Since 2004, there have been several
additional reports of diltiazem adulterated cocaine seizures in various
areas of the country. 2-6 When quantitated, the diltiazem content of these
seizures ranged from 8 to 20 %. These reports indicated that the reason
for the selection of diltiazem as an adulterant is unknown.
The cardiotoxic effects of cocaine include hypertension,
myocardial infarction, ventricular and supraventricular arrhythmias and
tachycardia. As a calcium channel blocker, diltiazem could potentially
offer some protection from the cardiac dysrhythmias induced by
cocaine. One study examined the interaction between calcium channel
blockers and cocaine in humans and found that pretreatment with
diltiazem did not affect cocaine induced increases in blood pressure,
heart rate, pupil size or subjective “high” ratings. 7
Although the reason for adulteration of cocaine with diltiazem is
unclear, the identification of diltiazem in a case may assist with identifying
the source of the illicit cocaine. While there could potentially be an
interaction between the two drugs, this trend is very recent in Maryland
and the data are too limited to determine if the use of diltiazem as a
cocaine adulterant has a role in cocaine-related death cases.
References:
1 Peters, DE. Diltiazem HCl: An Analytical Profile. Microgram Journal
2004;2(1-4):11
2 Cocaine Containing Diltiazem in Deer Park, Texas. Microgram
Bulletin 2005;38(12):181
3 Cocaine in Bamboo Sticks (From Guyana) at JFK Airport, New York.
Microgram Bulletin 2006;39(6):73
4 Diltiazem, Hydroxyzine, and Methylephedrine Identified in Separate
Shipments of Cocaine. Microgram Bulletin 2004;37(8):137
5 Cocaine Containing Diltiazem on the West Coast. Microgram Bulletin
2005;38(1):2
6 Unusually Sized and Packaged Cocaine Bricks in Rolla, Missouri..
Microgram Bulletin 2006;39(7):84
7 Rowbotham, MC, Hooker WD, Mendelson, J and Jones, RT. Cocaine-
Calcium Channel Antagonist Interactions. Psychopharmacology (Berl)
1987;93(2):152
Cocaine, Diltiazem, Postmortem
K42 General Unknown Screening of Drugs
and Toxic Compounds in Human Samples
Using a Hybrid Triple Quadrupole/Linear
Ion Trap LC/MS/MS System
Tania A. Sasaki, PhD*, Applied Biosystems, 850 Lincoln Centre Drive,
MS 430, Foster City, CA 94404; Pierre Marquet, PhD, Department of
Pharmocology-Toxicology, University Hospital, 2 Avenue Martin
Luther King, Limoges, 97042, France; and Joaquim Soares-Granja,
Applied Biosystems, 25 Avenue de la Baltique, Courtaboeuf, 91943,
France
After attending this presentation, attendees will learn about using
LC/MS/MS for a general toxicology screen. Sample preparation is
simplified versus other screening techniques. This general screening
technique also has the capability to detect unexpected drugs and
metabolites, as well as targeted analytes.
This presentation will impact the forensic community and/or
humanity by demonstrating a relatively new and novel screening
technique that is, in general, simple and faster compared to most
techniques. It allows faster and more specific detection and
identification of analytes in a screening assay.
* Presenting Author
General unknown screening (GUS) procedures in clinical or
forensic toxicology are used to detect and identify the exogenous
compounds present in human samples, whether expected or not. A
comprehensive LC/MS/MS GUS method has been developed for drugs,
toxic compounds and their respective metabolites in biological fluids
A simple, non-selective solid-phase extraction sample preparation
was used. The mass spectrometer is operated in the Information
Dependent Acquisition (IDA) mode, where ions are selected from a
single MS ion-trap survey scan and the two most intense ions are
submitted for MS/MS acquisition. The complete cycle time lasts
approximately 1.36 s. A library of MS/MS spectra of parent compounds
and metabolites has been built up and the MS/MS spectra acquired can
be searched against the library for analyte identification and
confirmation.
This method proved to be very efficient to identify unexpected
compounds in biological samples (as far as they corresponded to library
entries), as well as to give clues about the presence of metabolites owing
to MS similarities with their respective parent compound. More than
1000 MS/MS spectra in the positive mode and 250 in the negative mode
were entered in the library, together with compound name, developed
chemical structure, CAS number, retention time, relative retention time
and UV spectrum. Clinical cases will be presented where compounds
not found by other screening or target techniques could be identified
unambiguously.
A unique combination of the innovative operating modes offered by
hybrid triple-quadrupole linear ion-trap mass spectrometers and new
software features rendered it possible to develop a comprehensive and
efficient method for the General Unknown Screening of drugs, toxic
compounds, and metabolites in blood or urine.
Toxicology, LC/MS/MS, Drug Screening
K43 Determination of Alprazolam in Oral Fluid
Sumandeep Rana, MS, Cynthia Coulter, BS, Christine M. Moore, PhD*,
Michael J. Vincent, MS, and James Soares, PhD, Immunalysis
Corporation, 829 Towne Center Drive, Pomona, CA 91767
After attending this presentation, attendees will learn the
disposition of alprazolam in oral fluid and understand the degree of
sensitivity necessary for its detection.
This presentation will impact the forensic community and/or
humanity by demonstrating how, as oral fluid gains acceptance as a
suitable specimen type for roadside collection, procedures for the
detection of low level benzodiazepines are very important.
Methods: Oral fluid is increasingly being studied as a suitable
matrix for roadside collection and determination of driving under the
influence of drugs. A low dosage, potent benzodiazepine with anxiolytic
properties, alprazolam, was selected for this experiment, due to its
potential contribution to impaired driving. Benzodiazepines have not
been widely detected in oral fluid since the saliva:plasma (S:P) ratio is
less than 0.5 for most of the drug class. The newer benzodiazepines are
also given in low dosage regimens making their detection in oral fluid
even more difficult.
Extraction: Calibrators were prepared in Quantisal
transportation buffer at concentrations of 0.1, 0.2, 0.5, 1, 2 and 5 ng/mL
of alprazolam. Deuterated (d5) alprazolam was added at a concentration
of 5 ng/mL. Mixed mode (cation exchange:hydrophobic) solid phase
extraction columns were conditioned with methanol (3 mL), deionized
water (3 mL) and 0.1M phosphate buffer (pH 6.0; 2 mL). The specimens
were loaded onto the column and allowed to run through. The columns
were washed with deionized water (3 mL) and 0.1M phosphate
buffer:acetonitrile (80:20, v,v: 2 mL). The columns were dried for 5
minutes, then hexane (1 mL) was added. The alprazolam was eluted
with ethyl acetate:ammonium hydroxide (98:2 v,v; 2 mL) and
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