Abstract

The distribution of the nitrobenzodiazepines, flunitrazepam, clonazepam and nitrazepam, and their respective 7-amino metabolites were examined in blood, serum, vitreous humor, liver, bile and urine of decedents taking these drugs. Peripheral blood, serum and liver concentrations were not significantly different to each other. However, vitreous concentrations were one-third of blood, while bile concentrations were 5–12 fold higher. Blood, serum and vitreous contained predominantly the 7-amino metabolite, liver contained only the metabolite, while bile contained significant concentrations of both the parent drug and the 7-amino metabolite. Urine contained only small concentrations of parent drug, however, as expected a number of metabolites were detected. Redistribution studies compared the drug concentrations of femoral blood, taken at body admission to the mortuary, with femoral blood taken at autopsy approximately 39 h later in 48 cases. The concentrations of 7-amino metabolites were not significantly different, however the concentrations of parent nitrobenzodiazepines were significantly higher in the admission specimens. In 6 cases in which subclavian blood was taken, the concentrations were not significantly different to the concentrations in admission blood. Similar findings were observed when femoral and subclavian blood concentrations were compared in 6 cases. There was also no apparent difference in total blood concentrations of nitrobenzodiazepines when blood concentrations taken in hospital shortly prior to death were compared to postmortem blood. Postmortem diffusion into peripheral blood is therefore not a confounding factor in the interpretation of nitrobenzodiazepine concentrations.

References

1.
Drummer
O H
,
Ranson
D L
.
Sudden death due to benzodiazepines
.
Am J Forensic Med Pathol
(in press).
2.
Mattila
M AK
,
Larni
H M
.
Flunitrazepam: a review of its pharmacological properties and therapeutic use
.
Drugs
 0012-6667
1980
;
20
:
353
-
74
.
3.
Pinder
R M
,
Brodgen
R N
,
Speight
T M
,
Avery
G S
.
Clonazepam: a review of its pharmacological properties and therapeutic efficacy in epilepsy
.
Drugs
 0012-6667
1976
;
12
:
321
-
61
.
4.
Lloyd
J BF
,
Parry
D A
.
Forensic applications of the determination of benzodiazepine in blood samples by microcolumn cleanup and high-performance liquid chromatography with reductive mode electrochemical detection
.
J Anal Toxicol
1989
;
13
:
163
-
8
.
5.
Robertson
M D
,
Drummer
O H
.
Postmortem drug metabolism by bacteria
.
J Forensic Sci
1995
;
40
:
282
-
6
.
6.
Wickstrom
E
,
Amrein
R
,
Haefelfinger
P
,
Hartmann
D
.
Pharmacokinetic and clinical observations on prolonged administration of flunitrazepam
.
Eur J Clin Pharmacol
1980
;
17
:
189
-
96
.
7.
Drummer
O H
,
Horomidis
S
,
Kourtis
S
,
Syrjanen
M L
,
Tippett
P
.
Capillary gas chromatographic drug screen for use in forensic toxicology
.
J Anal Toxicol
1994
;
18
:
134
-
8
.
8.
Robertson
M D
,
Drummer
O H
.
An HPLC procedure for the measurement of nitrobenzodiazepines and their 7-amino-metabolites in blood
.
J Chromatog
1995
;
667
:
179
-
84
.
9.
Paterson
S
.
Drugs and decomposition
.
Med Sci Law
1993
;
33
:
103
-
9
.
10.
Agarwal
A
,
Lemos
N
.
Significance of bile analysis in drug-related deaths
.
J Anal Toxicol
1996
;
20
:
61
-
3
.
11.
Pounder
D J
,
Jones
G R
.
Postmortem drug redistribution—a toxicological nightmare
.
Forensic Sci Int
1990
;
45
:
253
-
63
.
12.
Prouty
W R
,
Anderson
W H
.
The forensic science implications of site and temporal influences on postmortem blood-drug concentrations
.
J Forensic Sci
1990
;
35
:
243
-
70
.
13.
Pounder
D J
.
The nightmare of postmortem drug changes
.
Legal Med Ann
1994
;
163
-
91
.
14.
Hilberg
T
,
Bugge
A
,
Beylich
K M
,
Mørland
J
,
Bjorneboe
A
.
Diffusion as a mechanism of postmortem redistribution. An experimental study in rats
.
Int J Legal Med
1992
;
105
:
87
-
91
.
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