Forensic Science International 325 (2021) 110893

Contents lists available at ScienceDirect

Forensic Science International

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

Case Report

Drug detection in decomposed cadavers confirms testimonial evidence in

a case of serial homicides ]]
]]]]]]
]]

⁎
Valeria Ottaviano a, Alessandro Mauro Tavone a, , Claudia Scipione a, Saverio Potenza a,
Giulia Petroni a, Gian Luca Marella b
a
University of Rome “Tor Vergata”, Department of Biomedicine and Prevention, via Montpellier 1, 00166 Rome, Italy
b
University of Rome “Tor Vergata”, Department of Surgical Sciences, via Montpellier 1, 00166 Rome, Italy

a r t i cl e i nfo a bstr ac t

Article history: Toxicology investigation on human’s buried dead bodies is a rare and challenging task in the forensic field.
Received 11 January 2021 As requested by the Judicial Authority, this work aimed to verify testimonial evidence that emerged during a
Received in revised form 21 June 2021 criminal investigation involving multiple murder cases. The statements indicated an improper medical
Accepted 29 June 2021
administration of one or more alleged drugs (propofol, morphine, diazepam, and midazolam) which pre-
Available online 30 June 2021
sumably caused the deaths. Since the supposed crimes took place several years before, the task of the
present work was to obtain results to support the charges. The analyses involved 18 biological samples
Keywords:
Propofol taken from four exhumed bodies, three of which were female and one male, each buried in a different date
Morphine and mode. Each sample was treated with specific purification and extraction techniques (LLE - SPE) after the
Diazepam addition of the deuterated analogs of the searched analytes (propofol-d17, morphine-d3, diazepam-d5,
Exhumation midazolam-d4) as internal standards. Afterwards, the extracts were subjected to qualitative analysis by gas
Human remains chromatography-mass spectrometry-Electron Impact (GC/MS - EI), both in full scan and SIM mode.
Decomposed cadavers Propofol, morphine, and diazepam were identified in the corpses. It supports testimonials that were ad-
GC-MS ministered just before the deaths occurred.
© 2021 Elsevier B.V. All rights reserved.

1. Introduction Given our circumstance to verify testimonial evidence of im-

Postmortem toxicology investigations on exhumed human re-
mains are not a frequent event, but a true challenge for both the
pathologist and the forensic toxicologist. Even more challenging is
the specific quest to confirm the administration of propofol, mor-
phine, diazepam, and midazolam.
Only few papers report the research of morphine in decomposed
organs, tissue, and hair [1–8].
No comparable situations are instead available for the other
molecules. Regarding propofol, there are several papers focused on
distinguishing between – or simply describing – suicidal, homicidal,
or accidental poisoning, together with the adopted analytical tech-
niques. In all cases the toxicological confirmation of this drug was
conducted on “fresh” fluids or tissues (blood, urine, bile, vitreous,
stomach content, brain, liver, adipose tissue, and cerebrospinal fluid)
from living traumatic patients or recently dead ones [9–29].
⁎
Corresponding author.
E-mail address: alessandromauro.tavone@students.uniroma2.eu (A.M. Tavone).
proper administration of alleged drugs in a case of serial homicides,
we report our forensic investigation experience along with tox-
icological procedure – involving conventional analytical chemistry
principles and the use of common forensic toxicology laboratory
devices – for determination of the above-mentioned molecules in
“non-conventional matrices” from exhumed bodies with long and
different postmortem intervals (PMI).
2. Case report
2.1. History
In 2019 we were committed by the Judicial Authority to find
forensic evidence supporting some witness statements collected
during a criminal investigation on a series of 4 aggravated murders
committed since 2014. From the initial reconstruction, it seems that
elderly people – already suffering from various comorbidities – ex-
perienced an acute episode at their domicile and required urgent
medical care. As stated by the Medical Report Forms, they all were
declared dead between 15 and 40 min after the beginning of the
EMTs interventions – which were always coordinated by the same

https://doi.org/10.1016/j.forsciint.2021.110893
0379-0738/© 2021 Elsevier B.V. All rights reserved.
V. Ottaviano, A.M. Tavone, C. Scipione et al. Forensic Science International 325 (2021) 110893

medical doctor. The eyewitnesses of the 4 cases all reported that the
victims died shortly after the doctor administered IV injections of a
milky solution, after which the clinical conditions of the patients
Duration of intervention

rapidly worsened. With exception of morphine in 3 out of 4 cases,

drugs injections were unrecorded.
According to the testimonies and the drug list in the medical
equipment, the drugs possibly involved were propofol (easy to
and death

identify because of the white color of the solution), morphine, dia-

39 min

20 min
24 min

15 min
zepam, and/or midazolam.
A summary of the four cases is presented in Table 1. It includes
the known medical history, date and duration of the last emergency
Nursing home

intervention and the administered therapy recorded in the med-

Location

ical form.
home

home

home

2.2. Exhumation and autopsy findings

The exhumation process took place one month after the request of
the judge. All the bodies were buried in different towns, and after ex-
humation the four coffins were all gathered in our institute of legal
O2 100% according to ALS protocol

medicine. Coffins were opened and complete autopsies were all con-
morphine 2 mg, adrenaline 1 fl,
Recorded Administered therapy

morphine 2 mg, Ringer 500 cc,

ducted the same day. Any violent cause of death has been excluded. In
Table 2 we summarize the PMI, the differences between the coffins, the
morphine 2 mg, O2 100%
Saline 500 cc, O2 100%

type of burial and the macroscopical preservation status of the bodies.

During the autopsies, a total of 29 biological matrices – consisting in
various fragment of organs, tissues, and fluids from all the corpses –
were collected separately in screw-capped scintillation vials, labeled,
weighed, sealed into individual tamper-proof envelopes and stored at in
none

a freezer − 20 °C for the further toxicological analyses.

2.3. Toxicological results

crisis was diagnosed. Hospitalization was not recommended as it was useless. Family members were not
History of colon cancer with liver and lung metastases and 1st degree AV block. The patient underwent a
History of a previous heart attack. The patient had a syncopal episode at home. He was found panting, in

History of type II diabetes and meningioma. The patient was found on the ground by her husband in their
resuscitate him, but to sedate him. Shortly thereafter, a respiratory blockage was developed, and death was

house. He was found in a state of coma, GCS 3 and gasping. A hemorrhagic stroke during a hypertensive
cardiorespiratory peri-arrest and with GCS 3, but without resumption of activity and consequent death.
History of heart disease and hypertension. The patient was assisted at home by the emergency service
called by telephone for illness. He was found in shock, GCS 10 and gasping conditions. Terminal septic

respiratory crisis in the nursing home where he resided. The emergency service doctor decided not to

informed about the administration of any therapy for palliative purposes. Shortly after the death was

2.3.1. Material and methods

2.3.1.1. Chemicals. Ethyl acetate, methanol, and isopropanol, all
analytical grade certified were purchased from Sigma-Aldrich. Strata-
X B and N Solid Phase Extraction Columns (SPEs) from Phenomenex.
Phosphate buffer 0.1 M at pH 7.4 was prepared in the laboratory with
shock is diagnosed, and circulatory support therapy initiated, but with no response.

deionized water (80 mΩ). Standard of morphine, diazepam, and

midazolam Cerilliant (purchased from Sigma-Aldrich) and standard
of propofol was purified by the generic drug provided by the
pharmaceutical company Kabi. Internal isotopic standards (propofol-
d17, morphine-d3, midazolam-d4, diazepam-d5) at a concentration
certified by the Cerilliant company were purchased from Sigma-
Aldrich. Enzyme β-glucuronidase/arylsulfatase from Helix pomatia
(Sigma-Aldrich). Bstfa (1% tmcs) derivatizing agent was purchased
from Supelco.

2.3.1.2. Sample preparation. Preliminarily, to evaluate the analytical

feasibility, we tested the biological specimens to understand their
nature, grade of decomposition, and hydrophilicity. Except for the
Medical history and last acute episode

thoracic fluid from case A, all the fluids collected were discarded
because mainly constituted by dissolved fats. (tested by adding 1 ml
of phosphate buffer 0,1 M a pH 7,4 after which fluids floated over the
water buffer, solidify at refrigeration at 4 °C and completely blended
with organic solvents). Since the investigated molecules are
metabolized in the liver and the organ was found in all four
corpses, aliquots of about 1,0 g of each liver were homogenized by
sonication in phosphate buffer pH 7,4 (2 × 1,5 ml x 30 min). The 3 ml
confirmed.
recorded.

fluids produced were then split in two aliquots one of which was
enzymatically hydrolyzed with β-glucuronidase/arilsulfatase from
Helix pomatia (Sigma-Aldrich). The same preparative procedure was
Age

adopted for the other organs and tissues collected. In two cases (Case
84

92

81
73

A and Case D) it was also possible to analyze the defrosting liquid

Sex
Case reports.

spontaneously formed due to the presence of hydrophilic intra or

M
F

extracellular fluid of the liver. Similarly, we could analyze the

Table 1

Case

defrosting liquids from the kidney of Case A and the spleen of

D
A

Case D.

2
V. Ottaviano, A.M. Tavone, C. Scipione et al. Forensic Science International 325 (2021) 110893

A total of 18 samples – listed in the results – were obtained for

Buried in an airy niche. Zinc sealed

Partial skeletonization of head and

face. Some red hair on the scalp.
Intact traditional Tyrolean dress,

Thoracic, pelvic, and abdominal

analysis.

with intact underlying skin.

Fluid in all serous cavities

2.3.1.3. Extraction. The determination of propofol was carried out in

organs distinguishable.
each sample for both the free and the total amount.
The free fraction research was performed on aliquots of the li-
quids and tissues’ homogenates added of the deuterated internal
coffin, intact.

standard (propofol-d17) and 0,1 M phosphate buffer at pH 7.4. The

total amount was measured on aliquots of the liquids and tissues’
Case D

515

homogenates added of propofol-d17 and 0,1 M phosphate buffer at

pH 7.4 after enzymatic hydrolysis with β-glucuronidase arylsulfatase.
Lungs, intestines, and pelvic organs

All the fluids were purified by liquid extraction with ethyl acetate,
Partial skeletonization of head and
face. Some dark hair on the scalp.
Black suit, intact. Underlying skin

substituted by a yellowish liquid.

Buried in an airy niche. Wooden

centrifugation, and careful evaporation to dryness at low tempera-

could not be separate from the

ture under nitrogen stream.

Fatty liver could be found.

For diazepam and midazolam, the investigation was made on

aliquots of the liquids and tissues’ homogenates with the addition of
appropriate deuterated internal standards (diazepam-d5 and mid-
azolam-d4), both before and after enzymatic hydrolysis with β-glu-
coffin, intact.

curonidase arylsulfatase and purified by liquid phase extraction with

clothes.

ethyl acetate after buffering at pH 7.4. For the morphine, the re-
Case C

495

search was conducted on aliquots of the liquids and homogenates of

tissues added with the deuterated internal standard (morphine-d3),
before and after enzymatic hydrolysis with β-glucuronidase ar-
Upper part of the dress preserved. Under the dress some dark

body. Some blond hair on small area of scalp still not detached.
Advanced, but incomplete, skeletonization of the rest of the

Abdominal and pelvic organ were can be easily pulverized.

ylsulfatase, after SPE extraction on Strata-X B polymeric columns.

Buried in the ground. Wooden coffin, almost completely

brown skin was still present, without subcutaneous fat.

2.3.1.4. Analysis. All the extracts underwent qualitative analysis

using gas chromatography-electron impact mass spectrometry in
scan mode and then they were monitored in SIM before and after
derivatization with bstfa-1% tmcs.
The analyses were conducted in gas chromatography-mass
spectrometry (GC/MS) in EI mode (Agilent mod. 6890 gas-chroma-
tograph combined with Agilent mod. 5973 mass spectrometer).
Capillary column HP5-MS 20 m, 0,25 mm i.d., 0,25 µm f.t., tem-
perature program between 100° (isothermal 2 min) e 300 °C (rate
20 °C/min). EI 70 eV, full scan between 40 and 500 a.m.u. Carrier gas
He. Single Ion Monitoring (SIM) as follows: propofol: m/z 163
(target), 178, 117; propofol-d17: m/z 177 (target), 195, 125. To further
disrupted

confirm propofol identification, the extracts were subsequently de-

Case B

rivatized with bstfa (1%tmcs) monitoring the following ions: pro-

954

pofol-TMS m/z 235 (target), 250; propofol-d17-TMS m/z 249 (target),

267; morphine-2TMS: m/z 429 (target), 236, 401; morphine-d3-
and brain absence. Dark hairs still on the scalp. Thoracic, pelvic
Some residues of clothes. Leathery skin covering the body. Eyes

and abdominal organs distinguishable. Fluid in pleural cavities.

2TMS: m/z 432 (target), 239, 404; diazepam: m/z 256 (target), 283,
221; diazepam-d5: m/z 261 (target), 287, 226; midazolam m/z 310
Buried in the ground. Wooden coffin, partially disrupted

(target), 325, 312; midazolam-d4: m/z 314 (target), 329, 316.

2.3.2. Results
The results from the forensic toxicology analyses are given in
Table 3. Please note that midazolam determination has been
performed when diazepam’s one took place. Results are omitted
because the determination was negative for all the samples.

3. Discussion

Confirming the eyewitnesses’ reports of unrecorded IV injection

of a milky colored solution just before the death, the analyses
identified the anesthetic drug propofol in at least one organ or fluid
Exhumation and autopsy findings.

of all four cadavers. The analyses mainly focused on the hepatic

Case A

tissue because of the peculiar pharmacokinetics of propofol, the

1235

absence of "conventional" biological fluids and the lack of biblio-

graphic references regarding the stability of the investigated mole-
cules and their determination in material coming from exhumation.
Type of burial

In fact, the liver is the organ where the metabolism of all the in-
Preservation
PMI (days)

vestigated molecules (propofol, morphine, diazepam, midazolam)

status

occurs, and fortunately remains of this organ were found in all four
Table 2

bodies. In the liver of all the decedents, propofol was identified even
after a single intravenous bolus and despite the differences in burial

3
V. Ottaviano, A.M. Tavone, C. Scipione et al. Forensic Science International 325 (2021) 110893

Table 3 going to die in the circumstances of the EMT interventions. On the

Results of drugs determination. other side, what is sure is that there was no therapeutic indication
Sample Propofol Diazepam Morphine for administration of propofol, which indeed have a direct link in the
A1 – liver 1 Positive Negative Positive
rapid worsening of clinical conditions of the 4 cases. Also, the sup-
A2 – liver 2 Positive Negative Positive position that the choice of propofol may be related to a terminal
A3 – hepatic Positive Not Performed Not Performed palliative sedation is mistaken: all international guidelines and sci-
defrosting liquid entific works recognize the use of short-time action benzodiazepines
A4 – thoracic fluid Positive Negative Negative
(like midazolam), opioids (morphine) and less frequently other se-
A5 – kidney Positive Negative Not Performed
defrosting liquid dative drugs (haloperidol, chlorpromazine) for this purpose, being
A6 - kidney Positive Negative Negative propofol not included [36–38]. However, a proper informed consent
A7 - bladder Positive Negative Negative is mandatory in such cases.
B1 – liver 1 Positive Positive Positive
B2 - liver 2 Positive Not Performed Negative
B3 - bladder Positivea Negative Negative
4. Conclusions
C1 – liver 1 Positive Negative Positive
C2 – liver 2 Positive Negative Positive The analysis of unconventional matrices such as those coming
C3 – scalp with hair Negative Not Performed Negative from exhumation and the absence of suitable reference data, do not
D1 – liver 1 Positive Negative Negative
allow the interpretation of the results obtained except to confirm, on
D2 – liver 2 Positivea Not Performed Negative
D3 - hepatic Positive Not Performed Negative an exclusively qualitative basis, that the alleged administration of
defrosting liquid unrecorded drugs took place.
D4 – splenic Positive Negative Not Performed From a forensic point of view, the above results supported the
defrostic liquid testimony (ambulance intervention forms and eyewitnesses) that all
D5 - spleen Not Performed Not Performed Negative
deaths occurred in a short time after the IV injection of a milky
In sample column, the letter indicate the case. solution. Given the pharmacology of propofol, our results also sup-
a
Metabolite PPF 1,4-QUINOL-TMS was identified infull scan.
port the thesis of a direct causal link between the administration and
the worsening of the subjects’ cardiac and respiratory conditions.
type and times of death. We opted to use isotopic internal standards
(deuterated, in this case) because there is the certainty that they are Compliance with ethical standards
not present in the organic material but, at the same time, the be-
havior in the organism is the same as the native molecule. The use of All procedures performed in the study involving human partici-
internal isotopic standards, therefore allowed us to carry out ex- pants were in accordance with the 1964 Helsinki declaration and its
periments aimed at evaluating the optimal extraction and the gas later amendments or comparable ethical standards, and with the
chromatographic conditions, as well as the linearity of the response ethical standards of our institutional research committee which gave
necessary for quantitative results obtained, but not presented in the us its due approval.
current work.
Results also showed differences about the injected drug “cock- Funding
tails” and on the quantitative propofol outcomes. Some practical
considerations can also be done. This research did not receive any specific grant from funding
An important indication that emerged from the quantitative as- agencies in the public, commercial, or not-for-profit sectors.
sessments here carried out is that, in all of the cases, there was no
significant difference between the concentrations of propofol mea- Declaration of Competing Interest
sured before and after enzymatic hydrolysis with β-glucuronidase
(free fraction vs total fraction). Suggesting, at least, a strong temporal The authors declare that they have no known competing fi-
link between the injection and the death. nancial interests or personal relationships that could have appeared
For case B as the liver appeared very “dry”, mainly consisting in to influence the work reported in this paper.
its stromal pattern, with the absence of parenchymal tissue and fats,
the best qualitative and quantitative recovery of the drugs was CRediT authorship contribution statement
achieved. In this case it was also possible to identify its hydroxy
metabolites and propofol at higher concentrations. Otherwise, in the Valeria Ottaviano: Conceptualization, Investigation, Methodology,
case of C, the biological matrices were particularly degraded and rich Validation, Resources, Project administration, Writing - review &
in interfering molecules. The liver was fatty with a high tendency to editing. Alessandro Mauro Tavone: Writing - original draft, Formal
form emulsions with the buffer. In addition to the liver, a fragment of analysis, Investigation. Claudia Scipione: Resources, Writing. Saverio
the scalp was also tested for propofol, morphine, diazepam and Potenza: Investigation, Resources. Giulia Petroni: Language editing,
midazolam providing negative results. We suppose that the subject's Writing and Revisioning, Resources. Gian Luca Marella: Investigation,
antemortem pathological condition (obese with metastatic liver Resources, Supervision.
cancer in the terminal phase) might have influenced both the poor
drugs distribution in life and the postmortem degradation processes, Conflit of interest
making the recovery of the molecules extremely difficult [30].
Differences measured in the four cadavers can reasonably be related The authors state that they have no conflit of interest.
to gender differences (one male and three females) [16], physical con-
stitution (body mass and fat content), preexisting pathophysiological References
situations (sepsis, bacterial flora, circulatory problems) survival interval
between the intravenous administration and the declaration of death [1] K. Worm, A. Steentoft, H. Christensen, Experiences in interpreta-tion with ex-
(15–40 min), burial times and modes [16,30–35]. humed material illustrated by a single case of morphine intoxica-tion, J. Forensic
Sci. Soc. 23 (3) (1983) 209–212, https://doi.org/10.1016/S0015-7368(83)72243-7
From a medico-legal aspect, the real causes of deaths can only be [2] B. Levine, S.C. Wu, A.M. Dixon, J.E. Smialek, An unusual mor-phine fatality,
supposed. All the victims were – from a clinical point of view – Forensic Sci. Int. 65 (1) (1994) 7–11, https://doi.org/10.1016/0379-0738(94)
critically ill patients, but that does not mean that they were surely 90294-1

4
V. Ottaviano, A.M. Tavone, C. Scipione et al.
[3] A.M. Tsatsakis, M.N. Tzatzarakis, D. Psaroulis, C. Levkidis, M. Michalodimitrakis,
Evaluation of the addiction history of a dead woman after exhumation and
sectional hair testing, Am. J. Forensic Med. Pathol. 22 (1) (2001) 73–77, https://
doi.org/10.1097/00000433-200103000-00015
[4] N. Raikos, H. Tsoukali, S.N. Njau, Determination of opiates in postmortem bone
and bone marrow, Forensic Sci. Int. 123 (2–3) (2001) 140–141, https://doi.org/10.
1016/s0379-0738(01)00529-1
[5] D.J. Pounder, The case of Dr. Shipman, Am. J. Forensic Med. Pathol. 24 (3) (2003)
219–226, https://doi.org/10.1097/01.paf.0000070000.13428.a3
[6] S. Cengiz, Ö. Ulukan, I. Ates, H. Tugcu, Determination of mor-phine in post-
mortem rabbit bone marrow and comparison with blood morphine concentra-
tions, Forensic Sci. Int. 156 (2) (2006) 91–94, https://doi.org/10.1016/j.forsciint.
2004.12.017
[7] C. Cattaneo, F. Gigli, F. Lodi, M. Grandi, The detection of morphine and codeine in
human teeth: an aid in the identification and study of human skeletal re-mains,
J. Forensic Odontostomatol. 21 (1) (2003) 1–5.
[8] H.M. Stevens, The stability of some drugs and poisons in putrefying human liver
tissues, J. Forensic Sci. Soc. 24 (1984) 577–589.
[9] O.H. Drummer, A fatality due to propofol poisoning, J. Forensic Sci. 37 (1992)
1186–1189.
[10] T.C. Chao, D.S. Lo, T.H. Koh, The first fatal 2, 6-diisopropylphenol (propofol)
poisoning in Singapore: a case report, Forensic Sci. Int. 66 (1994) 1–7.
[11] A. Roussin, et al., (Letter to the editor). Death related to a recreational abuse of
propofol at therapeutic dose range, Br. J. Anaesth. 97 (2006) 268.
[12] R.J. Levy, Clinical effects and lethal and forensic aspects of propofol, J. Forensic
Sci. 56 (2010) S142–S147, https://doi.org/10.1111/j.1556-4029.2010.01583.x
[13] S. Iwersen -Bergmann, Death after excessive propofol abuse, Int. J. Leg. Med.
114 (2001) 248–251.
[14] A.A. George, V.M. Hargrove, D.K. Molina, Postmortem propofol levels: a case of
residual detection long after administration, Am. J. Forensic Med. Pathol. 37 (1)
(2016) 4–6, https://doi.org/10.1097/PAF.0000000000000209
[15] R.J. Dinis-Oliveira, Metabolic profiles of propofol and fospropofol: clini-cal and
forensic interpretative aspects, BioMed Res. Int. 2018 (2018) 6852857, https://
doi.org/10.1155/2018/6852857
[16] E. Choong, I. Loryan, M. Lindqvist, Å. Nordling, S. el Bouazzaoui, R.H. van Schaik,
M. Ingelman-Sundberg, Sex difference in formation of propofol metabolites: a
replication study, Basic Clin. Pharmacol. Toxicol. 113 (2) (2013) 126–131, https://
doi.org/10.1111/bcpt.12070
[17] J. Salerno, Long-Term Detection of Propofol Glucuronide in Urine Follow-ing
Anesthetic Induction and Maintenance with Propofol Pharmacology & Pharmacy,
2013, 4, pp. 528–534.
[18] M.Y. Peeters, H. Kuiper, B. Greijdanus, J. van der Naalt, C.A. Knibbe, D.R. Uges, Gas
chromatography–mass spectrometric assay for propofol in cerebrospinal fluid of
traumatic brain patients, J. Chromatogr. B 852 (2007) 635–639.
[19] J. Guitton, M. Desage, A. Lepape, C.S. Degoute, M. Manchon, J.L. Brazier,
Quantitation of propofol in whole blood by gas chromatog-raphy-mass spec-
trometry, J. Chromatogr. B 669 (1995) 358–365.
[20] F. Vaiano, G. Serpelloni, M. Focardi, A. Fioravanti, F. Mari, E. Bertol, LC–MS/MS
and GC–MS methods in propofol detection: evaluation of the two analytical
procedures, Forensic Sci. Int. 256 (2015) 1–6.
Forensic Science International 325 (2021) 110893
[21] Han Eunyoung, A study of analytical methods for the determination of propofol
in blood, Arch. Pharm. Res. 37 (2014) 157–167.
[22] A. Orfanidis, A GC–MS method for the detection and quantitation of ten major
drugs of abuse in human hair samples, J. Chromatogr. B 1047 (2017) 141–150.
[23] S. Cox, J. Bailey, C. Okafor, R. Seddighi, T. Doherty, The influence of storage time
and temperature on propofol concentrations in canine blood and plasma, PeerJ
5 (2017) 3476, https://doi.org/10.7717/peerj.3476
[24] K.M. Krasinska, The effects of obesity on anesthetic drug distribution – ab-solute
quantitation of propofol in human plasma by GC-MS/MS, in: Proceedings of the
62nd ASMS Conference, June 15–19, Baltimore, MD, 2014.
[25] R.J. Levy, The Michael Jackson autopsy: insight provided by a forensic an-es-
thesiologist, J. Forensic Res. (2011) 2–8.
[26] J.S. Pyo, Selective and accurate determination method of propofol in hu-man
plasma by mixed-mode cation exchange cartridge and GC-MS, J. Anal. Methods
Chem. 2016 (2016) 9531769, https://doi.org/10.1155/2016/9531769 Epub 2016
Aug 11. PMID: 27597928; PMCID: PMC4997078.
[27] S.Y. Lee, N.H. Park, E.K. Jeong, J.W. Wi, C.J. Kim, J.Y. Kim, M.K. In, J. Hong,
Comparison of GC/MS and LC/MS methods for the analysis of propofol and its
metabolites in urine, J. Chromatogr. B 900 (2012) 1–10, https://doi.org/10.1016/j.
jchromb.2012.05.011 Epub 2012 May 17.
[28] W. Hikiji, K. Kudo, Y. Usumoto, A. Tsuji, N. Ikeda, A simple and sensitive method
for the determination of propofol in human solid tissues by gas chromato-
graphy-mass spectrometry, J. Anal. Toxicol. 34 (7) (2010) 389–393, https://doi.
org/10.1093/jat/34.7.389
[29] G. Roda, S. Arnoldi, M. Dei Cas, V. Ottaviano, E. Casagni, F. Tregambe, G.L. Visconti, F.
Farè, R. Froldi, V. Gambaro, Determination of Cyanide by Micro-diffusion Technique
Coupled to Spectrophotometry and GC/NPD and Propofol by Fast.
[30] A.M. Almulhim, R.G. Menezes, Evaluation of postmortem changes, StatPearls,
StatPearls Publishing, Treasure Island (FL), 2021, pp. 1–7, https://doi.org/10.
1093/jat/bky015 〈https://www.ncbi.nlm.nih.gov/books/NBK554464/〉GC/MS-
TOF in a Case of Poisoning. Journal of Analytical Toxicology, 2018.
[31] G. Skopp, Preanalytic aspects in postmortem toxicology, Forensic Sci. Int.
142 (2–3) (2004) 75–100, https://doi.org/10.1016/j.forsciint.2004.02.012
[32] R.E. Ferner, Post-mortem clinical pharmacology, Br. J. Clin. Pharmacol. 66 (4)
(2008) 430–443, https://doi.org/10.1111/j.1365-2125.2008.03231.x Epub 2008
May 29. PMID: 18637886; PMCID: PMC2561112.
[33] M. Kennedy, Interpreting postmortem drug analysis and redistribution in de-
termining cause of death: a review, Pathol. Lab. Med. Int. 7 (2015) 55–62, https://
doi.org/10.2147/PLMI.S65245
[34] O.H. Drummer, J. Gerostamoulos, Postmortem drug analysis: analytical and
toxicological aspects, Ther. Drug Monit. 24 (2) (2002) 199–209.
[35] M.C. Yarema, C.E. Becker, Key concepts in postmortem drug redistribution, Clin.
Toxicol. 43 (2005) 235–241.
[36] O.S. Rosengarten, Y. Lamed, T. Zisling, A. Feigin, J.M. Jacobs, Palliative sedation at
home, J. Palliat. Care 25 (1) (2009) 5–11 (Spring).
[37] D. Azoulay, R. Shahal-Gassner, M. Yehezkel, E. Eliyahu, N. Weigert, E. Ein-Mor,
J.M. Jacobs, Palliative sedation at the end of life, Am. J. Hosp. Palliat. Care 33 (4)
(2016) 369–373.
[38] L. Orsi, G.R. Gristina, Palliative sedation: the position statement of the Italian
National Committee for Bioethics, Minerva Anestesiol. 83 (2017) 524–528.