Recent applications of liquid chromatography-mass spectrometry in forensic science.

Recent years have seen the development of powerful technologies that have provided forensic scientists with new analytical capabilities, unimaginable only a few years ago. With liquid chromatography-mass spectrometry (LC-MS) in particular, there has been an explosion in the range of new products available for solving many analytical problems, especially for those applications in which non-volatile, labile and/or high molecular weight compounds are being analysed. The aim of this article is to present an overview of some of the most recent applications of LC-MS (/MS) to forensic analysis.

In vitro partition of irinotecan (CPT-11) in human volunteer blood: the influence of concentration, gender and smoking.

We have performed in vitro incubations of blood from male and female volunteers, smokers and non-smokers, with irinotecan at a gradient of different concentrations in order to investigate changes of partition between red blood cells (RBCs), total plasma and the free fraction. Since irinotecan (CPT-11) is not metabolized in vitro, there is no data available on its active metabolite SN-38. After extraction and sample pre-treatment, a validated high-performance liquid chromatography method followed by fluorescence detection was used to determine the concentration of the drug in the different blood constituents.

In vitro partition of docetaxel and gemcitabine in human volunteer blood: the influence of concentration and gender.

We have performed in vitro incubations of blood from male and female volunteers with gemcitabine and docetaxel alone, and in combination, at different concentration gradients in order to investigate changes in partition between red blood cells (RBCs), total plasma and the free fraction. After extraction and sample pre-treatment, a validated high-performance liquid chromatography method followed by UV detection was used to determine the concentrations of both drugs in the different blood constituents. The partition ratio [the concentration in the erythrocytes divided by the concentration in plasma (E/P)] was calculated.

The relevance of therapeutic drug monitoring in plasma and erythrocytes in anti-cancer drug treatment.

Therapeutic drug monitoring generally focuses on the plasma compartment only. Differentiation between the total plasma concentration and the free fraction (plasma water) has been described for a number of limited drugs. Besides the plasma compartment, blood has also a cellular fraction which has by far the largest theoretical surface and volume for drug transport.

Amount of self-reported illicit drug use compared to quantitative hair test results in community-recruited young drug users in Amsterdam.

Aims: To assess the dose-effect relationship between self-reported drug intake and the concentration of drugs and/or their metabolites in hair and to examine factors that may mediate this relationship.

Design And Setting: A cohort study among young drug users (YDU) in Amsterdam, the Netherlands, which began in July 2000. At intake, YDU were asked to report their average drug intake over a 2-month period.

Operant learning and differential-reinforcement-of-low-rate 36-s responding in 5-HT1A and 5-HT1B receptor knockout mice.

Previous studies with mice lacking 5-HT(1A) (1AKO) and 5-HT(1B) (1BKO) receptors in hippocampus-dependent learning and memory paradigms, suggest that these receptors play an important role in learning and memory, although their precise role is unclear. In the present study, 1AKO and 1BKO mice were studied in operant behavioural paradigms of decision making and response inhibition, to further study the putative involvement of these receptors in prefrontal cortex-dependent learning and memory. Moreover, because 1AKO mice have been shown to exhibit an antidepressant-like phenotype and 1BKO mice to be more impulsive in ethological studies, mice were trained in a differential-reinforcement-of-low-rates (DRL) procedure.

Autonomic changes associated with enhanced anxiety in 5-HT(1A) receptor knockout mice.

5-HT(1A) receptor knockout (KO) mice have been described as more anxious in various anxiety paradigms. Because anxiety is often associated with autonomic changes like elevated body temperature and tachycardia, radiotelemetry was used to study these parameters in wild type (WT) and KO mice in stress-/anxiety-related paradigms. Basal body temperature (BT), heart rate (HR), and their diurnal rhythmicity did not differ between well-adapted WT and KO mice.

GABA(A)-benzodiazepine receptor complex sensitivity in 5-HT(1A) receptor knockout mice on a 129/Sv background.

Previous studies in 5-HT(1A) receptor knockout (1AKO) mice on a mixed Swiss Websterx129/Sv (SWx129/Sv) and a pure 129/Sv genetic background suggest a differential gamma-aminobutyric acid (GABA(A))-benzodiazepine receptor complex sensitivity in both strains, independent from the anxious phenotype. To further investigate these discrepancies, various GABA(A)-benzodiazepine receptor ligands were tested in different behavioral paradigms in 1AKO and wild type (WT) mice on a 129/Sv background. 1AKO and WT mice responded comparably to alprazolam, flumazenil, alcohol and pentylenetetrazol as measured in the stress-induced hyperthermia paradigm.

5-HT(1B) receptor knockout mice show no adaptive changes in 5-HT(1A) receptor function as measured telemetrically on body temperature and heart rate responses.

Two presynaptic receptors play an important role in the regulation of serotonergic neurotransmission, i.e., the 5-HT(1A) and 5-HT(1B) receptor.

Hair analysis for cannabinoids and amphetamines in a psychosis incidence study.

It remains often uncertain whether the use of illicit substances has contributed to the aetiology of psychosis. Gas chromatography-mass spectrometry can be used to detect them in hair of the head. Given a monthly growth rate between 1.