Forensic Science International 219 (2012) 265–271

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Forensic Science International

journal homepage: www.elsevier.com/locate/forsciint

Evaluation of postmortem redistribution phenomena for commonly

encountered drugs
Eunyoung Han, Eunmi Kim, Hyojeong Hong, Sujin Jeong, Jihyun Kim, Sangwhan In,
Heesun Chung, Sangki Lee *
National Forensic Service, 331-1 Shinwol 7-Dong, Yang-Chun Gu, Seoul, South Korea

A R T I C L E I N F O A B S T R A C T

Article history: We described the findings of a study into the post-mortem redistribution (PMR) of 76 drugs found in 129
Received 11 August 2011 drug-related cases between 2006 and 2009. Seventy six drugs (psychotropic drugs (n = 14),
Received in revised form 2 January 2012 antidepressants (n = 9), sedatives (n = 6) and so on) were simultaneously quantified in cardiac and
Accepted 5 January 2012
peripheral blood by gas chromatography–mass spectrometry (GC/MS) or liquid chromatography–
Available online 30 January 2012
tandem mass spectrometry (LC/MS/MS). The absence, possibility or presence of PMR of drugs was
determined according to the ratios of cardiac to femoral blood concentrations (C/P ratios). Proxyphylline
Keywords:
(C/P ratio: 0.85) showed no PMR; carbamazepine was not subject to PMR; a potential for PMR of
Postmortem redistribution
Cardiac blood
lorazepam and mirtrazapine cannot be excluded; chlordiazepoxide is subject to PMR; acetaminophen
Peripheral blood and alprazolam exhibit minimal PMR; amitriptyline and benztropine exhibit PMR. Codeine (C/P ratio:
4.9), zolpidem (C/P ratio: 3.74), chlorpromazine (C/P ratio: 2.97), fluoxetine (C/P ratio: 2.83) and
propranolol (C/P ratio: 2.72) had the largest C/P ratios.
Postmortem drug concentrations showed variations depending on sampling sites and characteristics
of the drugs. It is continuously necessary to analyze commonly used or abused drugs in simultaneously
collected cardiac and peripheral blood to establish significant reference values for PMR. These findings
can be used to reach a conclusion about the cause and manner of death.
ß 2012 Elsevier Ireland Ltd. All rights reserved.

1. Introduction death, environment, sampling site, volume of distribution,

diffusion, redistribution in body cavities and drug metabolism
Forensic toxicologists analyze chemicals, drugs, toxins, or after death [19]. Blood collected at autopsy is a typical and
poisons in blood or tissue and provide clues to medical examiners important biological sample and consists of cardiac and peripheral
so that they can interpret the cause and manner of death. In such blood [8]. The cardiac blood concentrations are, in general, higher
cases, the ability to detect chemicals or drugs depends on the use of than peripheral blood concentrations and blood samples taken at
appropriate reference materials, analytical procedures, instru- different times after death may increase with time [2,19,20] while
ments, forensic toxicologists’ skills and so on. In particular, the the opposite trend has also been reported [5,21]. Postmortem drug
important issue is whether or not the concentrations of drugs in concentrations in peripheral blood were reported to be similar to
biological samples properly reflect the concentrations at the time antemortem drug concentrations; therefore many laboratories use
of death. Between death and specimen collection, drug concentra- peripheral blood such as femoral vein blood [2,6,16]. However, it is
tions in tissues, organs or body fluids may vary greatly. Changes in still questionable whether we can consider postmortem drug
drug concentrations in post-mortem may be caused by a number of concentrations in peripheral blood as antemortem drug concen-
factors (e.g. hydrolysis, bacterial activity and postmortem redis- trations in all cases [6]. In some early works, it was mistakenly
tribution (PMR)). PMR is one of many factors that may lead to thought that diffusion from cardiac tissue was the main source of
changes in drug concentrations after death. It was first reported by PMR. However, the works of many others have clearly shown that
Gee et al. [1] and many studies have been performed to prove the the major source of PMR is solid organs (for example liver and/or
occurrence of this phenomenon [2–18]. It was reported that drug lung) even though diffusion from cardiac tissue may make some
concentrations in the body may change according to the time of contribution to PMR [21,22]. If the importance of PMR is not
properly considered, a wrong interpretation of the cause of death
could be made. However, the comprehensive PMR data were not
* Corresponding author. Tel.: +82 2 2600 4910; fax: +82 2 2600 4919.
obtained in our institute until now and we had to rely on
E-mail address: skleedoc@korea.kr (S. Lee). previously published papers to interpret PMR.

0379-0738/$ – see front matter ß 2012 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.forsciint.2012.01.016
266 E. Han et al. / Forensic Science International 219 (2012) 265–271

The aim of this study is to measure the extent of postmortem methanol was added and then dried under a stream of nitrogen for 5 min. Acidic
drugs were eluted into test tubes with 3 mL of chloroform/acetone (1:1, v/v). Basic
redistribution for commonly encountered drugs by examining
drugs were eluted into test tubes with 3 mL of ethyl acetate/ammonium water
differences between simultaneously collected cardiac and periph- (98:2, v/v). After the drug elution, each column was rinsed with 4 mL of hexane and
eral blood concentrations and to provide drug-specific reference methanol. The columns were dried under a stream of nitrogen for 5 min. Elution
values of PMR. containing compounds were evaporated to dryness at 40 8C under nitrogen for
20 min and reconstituted with 100 mL methanol and 1 mL was injected into the
2. Methods capillary column of the GC–MS system. For LC/MS/MS system, the extract was
reconstituted with 150 mL of methanol, filtered and finally 20 mL was injected into
2.1. Chemicals and apparatus LC/MS/MS system. For propofol analysis, liquid–liquid extraction (LLE) was
performed using slightly modified method described in a previously published
Trimipramine-d3, thymol, disodium hydrogen phosphate and monosodium
paper [27]. One milliliter of blood samples was put into a 15-mL glass cap tube, and
phosphate were obtained from Sigma–Aldrich (MO, USA). Table 1 shows seventy six
50 mL of thymol (10 mg/mL) as the internal standard, 0.5 mL of 0.05 M phosphate
standards analyzed. Methanol, acetic acid, chloroform, acetone, ethyl acetate,
buffer (pH 6.0) and 0.2 mL of 0.1 M sodium hydroxide were added and mixed. Then
ammonium water, hexane, sodium hydroxide, sodium sulfate, ammonium formate,
5 mL of chloroform–ethylacetate (70:30, v/v) was added, and the mixture was
formic acid and acetonitrile were HPLC grade. SPE column (Bond Elut1 certify
placed on an inversion mixer for 30 min at 50 rpm. After centrifugation, an aliquot
capacity 3 mL) was purchased from Varian (CA, USA).
of the organic layer (lower layer) was transferred to glass vial containing sodium
sulfate to eliminate water. After centrifugation, the supernatant was transferred to
2.2. Sample collection test tube, evaporated to dryness under vacuum for 20 min and reconstituted with
100 mL methanol. One mL was injected into the capillary column of the GC–MS
The anatomical location of blood sampling can influence the drug concentration.
system.
After the femoral vein was ligated (tied-off) to prevent drawing blood down from
central blood vessels (e.g. inferior vena cava), femoral blood was collected. Cardiac
blood was collected from central blood vessels (inferior vena cava) after opening the 2.4. Instrumentation
chest and abdomen. All departments of forensic medicine in our country use the
2.4.1. Gas chromatography–mass spectrometry (GC/MS) system
same standardized procedures during autopsy including blood collection site and
The GC–MS system consisted of a Hewlett Packard 7683 series injector, HP 6890
blood sampling, and all toxicology analyses of samples taken during autopsy are
series GC system (Wilmington, DE, USA), and HP 5973 mass selective detector. The
performed at our institute. Matched post-mortem cardiac and femoral blood
column used (Agilent Technologies, Foster, CA, USA) was a fused silica capillary
specimens were collected in 50 mL plastic tubes and stored at 20 8C until analysis.
column (HP-5 MS capillary column, 30.0 m  250 mm  0.25 mm). The injector was
The standard or average time it might take between the body arriving at our facility
operated in the splitless mode; the injection volume was 1 mL; the injector
and the sample collection is approximately 3 h. We selected cases where one or
temperature was 250 8C; the ionization energy was 70 eV and the transfer line
more drugs were detected according to suspected intoxications.
temperature was 280 8C. Initial oven temperature was 80 8C, maintained for 1 min,
increasing at 20 8C/min to 290 8C and maintained at this temperature for 15 min.
2.3. Sample preparation The GC/MS was all operated in full scan mode (Table 2). For propofol analysis,
injector temperature was 200 8C. The oven temperature was held at 50 8C for 1 min,
We measured the drugs in the samples and evaluated PMR phenomena in cardiac
increased at 10 8C/min to 190 8C and maintained at 290 8C for 5 min. The GC/MS was
and peripheral blood from post-mortem cases in National Forensic Service (NFS)
also operated in full scan mode.
from 2006 to 2009. Sample preparation and method validation have been described
in previously published papers [23–26]. One milliliter of whole blood (triplicate)
was taken and 30 mL of internal standard (trimipramine-d3: 5 mg/mL) and 5 mL of 2.4.2. Liquid chromatography–tandem mass spectrometry (LC/MS/MS) system
0.05 M phosphate buffer (pH 6.0) were added, vortexed and sonicated for 15 min. The high-performance liquid chromatographic system consisted of an Agilent
After centrifugation for 10 min, the upper layer was poured into a test tube. SPE 1200 series binary pump. Drugs were separated on an AllureTM PFP Propyl 5 mm,
column was activated using 2 mL of methanol and 2 mL of 0.1 M phosphate buffer 50 mm  2.1 mm column (Restek, PA, USA). The separation of drugs was performed
(pH 6.0). The supernatants were poured onto the conditioned columns and allowed using a gradient of a mixture of eluent A (water/2 mM ammonium formate/0.2%
to drain. Each column was then washed with 1 mL of distilled water and 2 mL of formic acid) and eluent B (acetonitrile/2 mM ammonium formate/0.2% formic acid).
0.2 M acetic acid, and dried under a stream of nitrogen for 7 min. Fifty microliter of A gradient program was used and the percentage of organic solvent (%A:%B) was

Table 1
Seventy six standards obtained from Cerilliant or Sigma–Aldrich and respective pharmaceutical companies.

Source Drugs

Cerilliant or Sigma–Aldrich Acetaminophen, Alprazolam, Ambroxol, 7-Aminoflunitrazepam, Amitriptyline, Benztropine, Benzydamine,

Bromazepam, Bupivacaine, Caffeine, Carbamazepine, Chlordiazepoxide, Chlorpropamide, Chlorpheniramine,
Chlorpromazine, Clozapine, Codeine, Dextromethorphan, Diazepam, Diclofenac, Dihydrocodeine,
Diphenhydramine, Doxylamine, Flunitrazepam, Fluoxetine, Flurazepam, Haloperidol, Ibuprofen, Imipramine,
Isoniazide, Ketamine, Levomepromazine, Lidocaine, Lincomycin, Lorazepam, Methocarbamol, Methylephedrine,
Metoclopramide, Mirtazapine, Nordazepam, Nortriptyline, Oxycodone, Pentobarbital, Phenobarbital, Phenytoin,
Pethidine, Pheniramine, Phentermine, propofol, Propranolol, Quetiapine, Rifampicine, Salicylic acid, Sertraline,
Sildenafil, Sulfadiazine, Sulfamethoxazole, Terazosin, Thiopental, Tianeptine, Ticlopidine, Tramadol, Trazodone,
Triazolam, Trimebutine, Trimethoprim, Valproic acid, Venlafaxine, Zolpidem

Respective pharmaceutical companies Clotiazepam, Escitalopram, Iomeprol, Isopropylantipyrine, Orphenadrine, Proxyphylline, Tiropramide

Table 2
Classification of drugs detected and quantified by GC/MS and LC/MS/MS system.

Instrument Drugs

GC/MS (standard solution: 10 mg/L) Acetaminophen, Amitriptyline, Benztropine, Benzydamine, Bupivacaine, Caffeine, Carbamazepine,
Chlordiazepoxide, Chlorpropamide, Chlorpheniramine, Chlorpromazine, Clozapine, Codeine, Dextromethorphan,
Diazepam, Diclofenac, Dihydrocodeine, Diphenhydramine, Doxylamine, Fluoxetine, Ibuprofen, Imipramine,
Ketamine, Lidocaine, Methylephedrine, Metoclopramide, Mirtazapine, Nordazepam, Nortriptyline, Orphenadrine,
Oxycodone, Pentobarbital, phenobarbital, Phenytoin, Pethidine, Pheniramine, Phentermine, Propofol, Propranolol,
Proxyphylline, Sertraline, Thiopental, Tramadol, Trimethoprim, Valproic acid, Venlafaxine, Zolpidem

LC/MS/MS (standard solution: 1 mg/L) Alprazolam, Ambroxol, 7-Aminoflunitrazepam, Bromazepam, Clotiazepam, Escitalopram, Flunitrazepam,
Flurazepam, Haloperidol, Iomeprol, Isoniazide, Isopropylantipyrine, Levomepromazine, Lincomycin, Lorazepam,
Methocarbamol, Quetiapine, Rifampicine, Salicylic acid, Sildenafil, Sulfadiazine, Sulfamethoxazole, Terazosin,
Tianeptine, Ticlopidine, Tiropramide, Trazodone, Triazolam, Trimebutine
 E. Han et al. / Forensic Science International 219 (2012) 265–271 267

changed linearly as follows: 0 min, (90:10); 10 min, (10:90); 15 min, (10:90); We observed no postmortem redistribution of carbamazepine
15.5 min, (90:10); 17.5 min, (90:10).
and proxyphylline and suggested that cardiac blood can be
The mobile phase was delivered through the column at a flow rate of 100 mL/
min. MS/MS data were acquired using a 3200 Q trap (Applied Biosystems, MDS substituted for peripheral blood when it is unavailable or scant
Sciex, CA, USA), hybrid triple quadrupole-linear ion trap mass spectrometer, in the quantitative analysis of them. Lalonde and Wallage [41]
equipped with Turbo VTM ion source. The instrument was operated in positive ion observed that marked differences between heart and femoral
mode with an electrospray ionization (ESI) source. Argon was used as collision gas blood ketamine concentrations and discussed that this may be
at 1.5 mTorr. For all compounds, spray voltage was set at 4.0 kV. Compounds were
quantitated in multiple reaction monitoring (MRM) mode (Table 2) and the
indicative of incomplete distribution prior to death and a rise as the
collision energy was set at 35 eV. result of PMR. And they concluded that the heart blood
concentration would better reflect the extent of drug action at
2.5. Statistical analysis these sites than a peripheral blood concentration because
Statistical analysis on drug concentrations in cardiac and peripheral blood was ketamine’s toxicities include depression of the respiratory center
performed using Statistical Package for the Social Sciences (SPSS) Version 10. of the brain and cardiac toxicity.
As shown in Fig. 1, codeine, zolpidem, chlorpromazine,
3. Results and discussions fluoxetine and propranolol had the largest C/P ratios. Drugs with
higher ratios seem to have a greater potential for PMR. Some
We evaluated PMR phenomena in simultaneously collected authors [22,70] suggested that high C/P ratios were due to the
cardiac and peripheral blood from post-mortem cases (n = 129). diffusion from the stomach and/or gastrointestinal tract or agonal
One to six drugs in each case were detected and 76 kinds of drugs aspiration of the vomited gastric content. Bynum et al. [22]
were quantified. Table 3 shows drugs that were detected and reported that tramadol does not appear to show significant
quantified in cardiac and peripheral blood and the ratios of cardiac postmortem redistribution, but they observed very high C/P ratio
to femoral blood concentrations (C/P ratios). Frequently detected of 5.0 and suggested diffusion from the stomach and/or
drugs of no. 1–33 are results from two or more of our cases. For gastrointestinal tract. Pragst et al. [70] found that diphenhydra-
remaining drugs, the interpretation of PMR was not performed mine concentrations in heart blood were much higher than in
because of statistical limitation (n = 1). femoral blood in some of the deaths because of agonal aspiration of
Studies on amitriptyline [4,18,28,31,33,34,54,55], carbamaze- the vomited gastric content.
pine [28,30,31,36,37], tramadol [22,46,56–59] and trazodone [47– The variation in C/P ratios of codeine, chlorpromazine,
49,60–63] related deaths and PMR have frequently been reported. zolpidem, diphenhydramine, propranolol and chlropheniramine
Propofol related deaths [64–69] have frequently been reported, but was high while that of proxyphylline, acetaminophen, carbamaz-
studies on PMR of propofol have not been reported. As for diclofenac, epine and phenobarbital was low (Fig. 1). Quantification accuracy
drug-related fatalities and PMR have rarely been reported and (CV of quantification) should be considered when we interprete C/
research about PMR of proxyphylline has not been reported. P ratios, the variation in C/P ratios and PMR phenomena.
Therefore, our data on PMR of propofol, diclofenac and proxyphyl- Drug properties such as volume of distribution, lipophilicity,
line could provide a useful reference for interpretative purposes. and pKa are important factors that affect PMR [17]. The apparent
The absence, possibility or presence of PMR of drugs was volume of distribution is defined as the amount of drug in the body
determined based on our results as follows; proxyphylline showed divided by plasma or blood concentration at distribution
no PMR; carbamazepine was not subject to PMR; a potential for equilibrium [30]. A volume of distribution of more than 3–4 L/
PMR of lorazepam and mirtrazapine cannot be excluded; kg indicates that a drug is liable to PMR [17,30]. Johnson et al. [71]
chlordiazepoxide is subject to PMR; acetaminophen, alprazolam, reported that PMR of fluoxetine with large volumes of distribution
orphenadrine, phenobarbital, tramadol, triazolam, valproic acid may account for larger CV. Drugs that exhibit minimal PMR in this
and venlafaxine exhibit minimal PMR; amitriptyline, benztropine, study have generally low volumes of distribution. Drugs with low
bromazepam, chlorpheniramine, chlorpromazine, codeine, diaze- volume of distribution are generally not associated with marked
pam, diclofenac, diphenhydramine, doxylamine, fluoxetine, keta- PMR [47]. However, the volumes of distribution of codeine and
mine, lidocaine, nordazepam, nortriptyline, propofol, propranolol, zolpidem are 2.2 and 0.6, respectively but C/P ratio was relatively
sertraline, trazodone and zolpidem exhibit PMR. high. Conversely, the volumes of distribution of nortriptyline,

C/P ratios
12 Vd 25

10
20
average of C/P ratio

8
volume of
distrib
ibution(L/K
ti (L/Kg)) 15

10
4

5
2

0 0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33
drugs

Fig. 1. Distribution of C/P ratios and volume of distribution (Vd) of frequently detected drugs. 1, codeine; 2, zolpidem; 3, chlorpromazine; 4, fluoxetine; 5, propranolol; 6,
benztropine; 7, trazodone; 8, diphenhydramine; 9, doxylamine; 10, nortriptyline; 11, ketamine; 12, chlorpheniramine; 13, bromazepam; 14, nordazepam; 15, sertraline; 16,
diazepam; 17, propofol; 18, diclofenac; 19, mirtazapine; 20, amitriptyline; 21, lorazepam; 22, orphenadrine; 23, chlordizaepoxide; 24, valproic acid; 25, lidocaine; 26,
alprazolam; 27, tramadol; 28, triazolam; 29, venlafaxine; 30, acetaminophen; 31, carbamazepine; 32, phenobarbital; 33, proxyphylline.
268 E. Han et al. / Forensic Science International 219 (2012) 265–271

Table 3
The C/P ratios (postmortem cardiac and femoral blood concentration) and postmortem redistribution of drugs.

Drugs Average C/P ratios (range) Case numbers (n) Reference PMR of drugs

1) Acetaminophen 1.3 (0.7–2.8) 37 [28] May exhibit PMR

1.5(1.1–2.5) 4 [29]
1.0 [30]a
1.06 (0.99–1.18) 3 Our data Exhibit minimal PMR
2) Alprazolam 1.5 (1.0–2.8) 4 [28] May exhibit PMR
0.9 (0.5–1.3) 9 [31]
0.9 1 [32]b
1.19 (1.00–1.37) 2 Our data Exhibit minimal PMR
3) Amitriptyline 3.1 (0.6–15) 30 [31] Is subject to PMR
1.36 (0.73–2.50) 13 Our data May exhibit PMR
4) Nortriptyline 2.2 (0.2–9.6) 43 [31] May exhibit PMR
2.3 (0.5–8.4) 28 [33]
2.5 (0.7–12) 20 [28]
12 1 [34]
2.01 (0.40–5.63) 12 Our data May exhibit PMR
5) Benztropine 1.3 (1.0–2.1) 5 [28] May exhibit PMR
2.5 (0.6–7.7) 11 [31]
2.17 (1.00–4.67) 4 Our data May exhibit PMR
6) Bromazepam 1.5 (0.8–4.2) 6 [28] May exhibit PMR
0.86 20 [35] No PMR
1.91 (1.49–2.33) 2 Our data May exhibit PMR
7) Carbamazepine 0.9 (0.4–1.0) 12 [28] Apparently is not subject to PMR
1.0 (0.8–1.1) 4 [31]
1.1 6 [30]c
1.1 1 [36] The slight rise in drug concentration
1.2 [37]
0.97 (0.74–1.16) 4 Our data Is not subject to PMR
8) Chlordiazepoxide 1.0 (0.5–1.4) 14 [28] Apparently does not exhibit PMR
1.27 (0.77–1.96) 4 Our data Is subject to PMR
9) Chlorpheniramine 3.1 (1.0–7.0) 4 [28] May exhibit PMR
1.2 (0.6–1.9) 6 [31]
1.93 (1.00–5.00) 6 Our data May exhibit PMR
10) Chlorpromazine 4.0 (1.0–8.0) 5 [28] May exhibit PMR
2.0 (0.8–7.2) 6 [31]
2.97 (0.81–7.06) 3 Our data May exhibit PMR
11) Codeine 2.3 and 3.5 2 [33] May be subject to PMR
1.4 (0.6–3.8) 21 [31]
1.8 (0.7–11) 24 [28]
4.90 (1.14–8.67) 2 Our data May exhibit PMR
12) Diazepam 1.6 (0.2–12) 46 [28] May exhibit PMR
1.3 (0.3–3.1) 38 [31]
1.62 (0.44–4.40) 18 Our data May exhibit PMR
13) Nordazepam 0.95 20 [35]
1.79 (0.62–3.74) 13 Our data May exhibit PMR
14) Diclofenac 1.54 (0.60–2.48) 2 Our data May exhibit PMR
15) Diphenhydramine 2.4 (0.4–6.0) 7 [33] Is subject to PMR
2.3 (0.8–21) 32 [28]
1.1 (0.3–4.3) 38 [38]b
2.09 (0.77–5.83) 8 Our data May exhibit PMR
16) Doxylamine 3.8 (0.6–13) 6 [31] May exhibit PMR
2.08 (0.86–5.67) 15 Our data May exhibit PMR
17) Fluoxetine 3.5 and 4.5 2 [39] Is apparently subject to PMR
2.9 (1.2–5.4) 5 [28]
2.4 (0.6–5.9) 21 [31]
6.2 1 [40]
2.83 (1.33–4.00) 5 Our data May exhibit PMR
18) Ketamine 1.6 (0.8–2.3) 2 [28] May exhibit PMR
3.3 (2.7–3.8) 2 [41]
1.95 (1.39–2.50) 2 Our data May exhibit PMR
19) Lidocaine 1.8 1 [33]
1.20 (1.00–1.43) 5 Our data May exhibit PMR
20) Lorazepam 1.0 (0.8–1.1) 2 [28] Apparently does not exhibit PMR
1.33 (1.00–1.67) 4 Our data Potential for PMR cannot be excluded.
21) Mirtazapine 1.0 (0.3–1.7) [31] Apparently does not exhibit significant PMR
1.1(0.75–1.7) 6 [42] Little PMR
1.3 5 [43] Potential for PMR cannot be excluded.
1.52 (0.76–2.60) 5 Our data Potential for PMR cannot be excluded.
22) Orphenadrine 1.7 and 2.0 [28] May exhibit PMR
2.3 (1.1–5.2) 5 [31]
1.31 (1.00–1.62) 2 Our data May exhibit PMR
23) Phenobarbital 1.1 (1.0–1.3) 8 [28] Exhibits minimal PMR
0.96 (0.79–1.25) 6 Our data Exhibits minimal PMR
24) Propofol 1.57 (0.86–2.97) 8 Our data May exhibit PMR
25) Propranolol 2.5 (1.0–3.8) 5 [28] May exhibit PMR
2.72 (1.00–3.63) 2 Our data May exhibit PMR
26) Proxyphylline 0.85 (0.79–0.90) 2 Our data No PMR
 E. Han et al. / Forensic Science International 219 (2012) 265–271 269

Table 3 (Continued )

Drugs Average C/P ratios (range) Case numbers (n) Reference PMR of drugs

27) Sertraline 0.9 (0.6–1.4) 5 [44] May exhibit PMR

2.5 (0.4–9.2) 16 [31]
1.0–4.8 2 [40]
1.73 (1.00–2.53) 4 Our data May exhibit PMR
28) Tramadol 1.1 (0.6–1.4) 6 [45] Does not appear to exhibit significant
and consistent PMR
1.36 1 [46]
1.4 (0.6–2.1) 9 [31]
1.18 (0.72–2.12) 17 Our data Exhibits minimal PMR
29) Trazodone 1.5 (1.3–1.9) 4 [47] May exhibit PMR
1.5 (0.6–4.8) 14 [31]
4 1 [48]
2 [49] Found no significant differences between
heart and femoral blood levels
2.14 (1.07–3.88) 3 Our data May exhibit PMR
30) Triazolam 2.8 (1.0–7.5) 4 [28] May exhibit PMR
1.61 1 [50]
1.17 (1.00–1.50) 3 Our data Exhibits minimal PMR
31) Valproic acid 1 1 [28]
1.24 (0.91–1.82) 3 Our data Exhibits minimal PMR
32) Venlafaxine 1.5 (0.9–2.1) 6 [31] May exhibit PMR
1.3–1.8 2 [51]
1.8 1 [52]b
0.90–5.5 4 [40]
1.15 (0.75–1.50) 3 Our data Exhibits minimal PMR
33) Zolpidem 0.8–0.9 3 [53] Does not appear to exhibit marked PMR
1.5 (1.1–2.0) 8 [31]
1.4 1 [21]
3.74 (0.67–13.25) 17 Our data May exhibit PMR
Ambroxol 1.23 1 Our data
7-Aminoflunitrazepam 0.75 1 Our data
Benzydamine 0.79 1 Our data
Bupivacaine 0.86 1 Our data
Caffeine 1.10 1 Our data
Chlorpropamide 1.21 1 Our data
Clotiazepam 1.00 1 Our data
Clozapine 5.44 1 Our data
Dextromethorphan 2.00 1 Our data
Dihydrocodeine 1.50 1 Our data
Escitalopram 1.65 1 Our data
Flunitrazepam 0.55 1 Our data
Flurazepam 1.00 1 Our data
Haloperidol 1.33 1 Our data
Ibuprofen 0.96 1 Our data
Imipramine 3.07 1 Our data
Iomeprol 2.25 1 Our data
Isoniazide 0.88 1 Our data
Isopropylantipyrine 1.08 1 Our data
Levomepromazine 1.50 1 Our data
Lincomycin 1.73 1 Our data
Methocarbamol 1.47 1 Our data
Methylephedrine 2.00 1 Our data
Metoclopramide 1.07 1 Our data
Oxycodone 1.04 1 Our data
Pentobarbital 1.22 1 Our data
Pethidine 1.27 1 Our data
Pheniramine 2.56 1 Our data
Phentermine 0.99 1 Our data
Phenytoin 0.56 1 Our data
Quetiapine 0.74 1 Our data
Rifampicine 1.06 1 Our data
Salicylic acid 1.19 1 Our data
Sildenafil 1.20 1 Our data
Sulfadiazine 0.93 1 Our data
Sulfamethoxazole 1.07 1 Our data
Terazosin 1.00 1 Our data
Thiopental 2.17 1 Our data
Tianeptine 2.26 1 Our data
Ticlopidine 0.81 1 Our data
Tiropramide 3.56 1 Our data
Trimebutine 2.00 1 Our data
Trimethoprim 1.12 1 Our data
a
Postmortem to antemortem heart blood for animals.
b
Cardiac/subclavian.
c
For the animals.
270 E. Han et al. / Forensic Science International 219 (2012) 265–271

sertraline and amitriptyline are 20, 20 and 12, respectively, but C/P death and blood collection and drug concentrations in tissue are
ratios were relatively low. Abernethy et al. [72] found that needed in further study.
acetaminophen Vd was increased in obesity and in men relative to
women and acetaminophen clearance increased with body weight
and was much greater in obese patients and in men. We can Acknowledgements
estimate that C/P ratio may increase in obese man in acetamino-
phen post-mortem cases because PMR is reportedly affected by Vd. This study was supported by the research & Development
Tissue-bound tricyclic antidepressants (TCAs) such as amitrip- Program for new technology of Forensic Science by the Ministry of
tyline, nortriptyline and mirtazapine may cause falsely elevated Public Administration and Security, Korea.
postmortem blood levels [55]. Some authors concluded that liver
TCA concentrations should be quantitated to clarify manner of
death to prevent interpretation of falsely elevated postmortem References
blood levels of TCA [54,55,73]. Moore et al. [43] reported the
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