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Examination of Firearms Review: 2007 to 2010 - Interpol

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CYP3A4, resulting in inhibited metabolism <strong>of</strong> other drugs and medicines, as<br />

well as compromised metabolism in poor metabolisers for CYP2D6. In addition,<br />

these drugs could cause various drug-drug interactions [528,529]. Furthermore,<br />

BZP and TFMPP inhibited each other's metabolism [529]. The metabolite ratio<br />

<strong>of</strong> amitriptyline (AT), nortriptyline (NT), and its 10-hydroxy metabolites was<br />

examined by LC-MS in hair samples <strong>of</strong> 23 white infants after long-term<br />

administration <strong>of</strong> AT [530]. High inter-individual variation <strong>of</strong> the metabolite<br />

ratios was observed and could be explained for those being CYP2C19 poor<br />

metabolizers, where the demethylation capabilities were depleted significantly.<br />

To study the metabolism <strong>of</strong> naloxone, an LC-MS/MS method was developed<br />

for determination <strong>of</strong> naloxone and its metabolite, nornaloxone, in plasma, urine,<br />

and human liver microsomes. When cDNA-expressed P450s were incubated<br />

with 20 ng <strong>of</strong> naloxone, nornaloxone formation was detected for P450s 2C18,<br />

2C19, and 3A4 [479]. Two cases were studied in which there was a suspicion<br />

that the patients continued <strong>to</strong> abuse diazepam, because <strong>of</strong> repeatedly positive<br />

urine test results. The measurement <strong>of</strong> diazepam metabolites in urine showed<br />

that none <strong>of</strong> them had in fact ingested diazepam during the study period [531].<br />

One <strong>of</strong> the subjects was found <strong>to</strong> have a slow metabolism for CYP2C9 as well<br />

as for CYP2C19. In the second case, there was a possible drug interaction<br />

between diazepam and zolpidem.<br />

4. Conclusions<br />

Phenomenal progress has been achieved in various areas relevant <strong>to</strong> forensic<br />

<strong>to</strong>xicology. The increased availability <strong>of</strong> more sensitive and specific<br />

instrumentation has enabled the development <strong>of</strong> many effective methods for<br />

the detection <strong>of</strong> a wider scope <strong>of</strong> drugs and/or their metabolites at very low<br />

levels, in both conventional and alternative specimens.<br />

With the more structured approach <strong>to</strong>wards control over illicit drug use while<br />

driving, the list <strong>of</strong> drugs that can be determined is continously expanding. It is<br />

known that the problem <strong>of</strong> DUID is far more complex than that <strong>of</strong> DUI, and that<br />

it still requires a large amount <strong>of</strong> research in various areas such as<br />

epidemiology, behavior, and <strong>to</strong>xicology. The efforts made in harmonization <strong>of</strong><br />

methods will undoubtedly facilitate more efficient cross-study comparisons in<br />

future drugged driving research.<br />

The development <strong>of</strong> methods for detection <strong>of</strong> alcohol biomarkers such as EtG,<br />

EtS and FAEE in oral fluid, urine, blood, vitreous humor, and hair has shed<br />

685

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