© Benaki Phytopathological Institute
Kasiotis & Machera
40
by liquid chromatography high-resolution
mass spectrometry (LC-HRMS) using an
Obritrap system. HRMS has already proved
its effectiveness in the drug discovery do-
main (Ramanathan
et al
., 2011), in metabo-
lomics studies (Xiao
et al
., 2012) and recently
was reported in human exposure evaluation.
This approach made effective the investiga-
tion of molecules on the basis of the theo-
retical mass of their quasi-molecular ions.
Nineteen metabolites of IMI were screened.
Nevertheless, no residues were detected.
Case Reports
Case reports usually refer to intentional
(suicide attempts) ingestion of an amount of
a pesticide formulation, a severe problem,
especially in developing countries (Gunnell
and Eddleston, 2003). Increased risk of sui-
cide with exposure to pesticides has been
reported particularly in intensive agricultur-
al regions (Parron
et al
., 1996). The latter is
becoming critical considering the risk pro-
jected to young people in these areas that
have relative easy access to pesticides for-
mulations (Kong and Zhang, 2010). Sever-
al case reports are published where NNDs
are implicated. Typical symptoms-man-
ifestations that develop in humans after
such exposure to NNDs are disorientation,
drowsiness, dizziness, cough, vomiting and
abdominal pain. In the case of non-fatal in-
cidents, after an initial treatment in the hos-
pital (nasogastric lavage, instillation of ac-
tivated charcoal), the patients are treated
symptomatically and supportive, and final-
ly discharged.
Wu
et al.
(2001) have presented a case re-
port of acute poisoning with IMI formula-
tion. More specifically a 64-year-old farmer
was attempted to suicide using a bottle of
insecticide containing IMI in
N
-methyl pyr-
rolidone (NMP), and a low percent of sur-
factant. The researchers concluded that it
was rather difficult to determine whether
the symptoms of drowsiness and dizziness,
were provoked by IMI. However, the rela-
tive high concentration of the solvent (NMP)
seemed to play a decisive role in intoxica-
tion. Proenca
et al.
(2005) published work
on the fatal poisoning with IMI. To assess ex-
posure in post-mortem samples the authors
developed an LC-DAD-ESI/MS method that
was capable to detect IMI and two of its me-
tabolites (6-CNA and 5-OH-IMI). Samples of
blood, urine and tissues were collected for
toxicological analysis. Sample preparation
was based on LLE with dichloromethane
as organic solvent. Analysis was conduct-
ed by concomitant use of diode array (DAD)
and mass spectrometer detector. IMI was
detected in all post-mortem samples, but
none of its two metabolites was detected.
All specimens prior to targeted IMI and me-
tabolites analysis were subjected to screen-
ing of other substances as well. None drug
or pesticide was found in the samples. From
analytical standpoint, the method was sen-
sitive, exhibiting an LOD of 0.002 μg/mL
blood
and LOQ of 0.01 μg/mL
blood
. Respective limits
in urine were not reported. IMI levels varied
from 0.29 μg/mL (in urine) to 2.05 μg/mL in
blood. Conclusively, this study demonstrat-
ed how analytical methodologies could as-
sist the resolving of cases that under routine
examinations is difficult to understand the
causative agents.
David
et al.
(2007) reported an incident
regarding IMI poisoning. More specifically,
a 22-year-old male with clinical toxicity was
hospitalized after ingestion of 30 mL of IMI
(17.8% concentration). Symptoms were as
those abovementioned, and the patient was
released on the 5
th
hospital day. Mohamed
et al.
(2009) published incidents from Sri
Lanka, where IMI was involved after inten-
tional self-poisoning (Mohamed
et al
., 2009).
The latter was an outcome of a prospective
observational cohort study of all poisoning
presentations that was established during
2002 and lasted until 2007. More precisely,
blood samples were taken, whenever possi-
ble so as to determine IMI levels (none me-
tabolite were included). Plasma was isolated;
SPE extracted, and the extract was subject-
ed to LC-MS/MS analysis. Over this period,
68 patients were presented with a history of
IMI exposure. Seven cases were occupation-
al dermal exposure and not worrying, five
involved co-ingestion of IMI with another
