Antidepressants Benzodiazepines Opiates Toxicological cases

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  Research topics related to forensic toxicology: 


Antidepressants

Depression is the most common psychiatric disorder in this century. Several chemical unrelated agents have been developed and introduced in the past decade to supplement the earlier antideressants (TCA’s).  These include inhibitors of the reuptake of serotonin or noradrenaline or both, as well as drugs with distinct neurochemical profiles.All antidepressants, that are currently available for clinical use, are effective for the treatement of depression, but vary significantly in terms of tolerability and side effects at therapeutic doses as well as life-threatening toxicity following overdose.Selective serotonin – and serotonin norepinephrine reuptake inhibitors, although much safer than TCA’s and MAO’s, are limited by tree factors:  side effects, response failure in patients with severe depression (which mostly leads to suicide) and drug-drug interactions.

A lot of  the drug-drug interactions are due to the fact that selective serotonin reuptake inhibitors (which are substrates for or inhibitors of Cyp-enzymes) are often administered in combination with other neuropsychiatric drugs, such as benzodiazepines, antipsychotics, anticonvulsants and even other antidepressants, which are substrates for one or more Cyp-enzymes.That’s why determination of antidepressants and their metabolites in biological fluids could be interesting in (forensic) toxicological analysis.The goal of this research is to achieve a selective and sensitive analytical method for the newer types of antidepressants in plasma and urine with GC/MS.

(By Sarah Wille)


Former research topics

 Low dosed benzodiazepines

Benzodiazepines are frequently prescribed drugs which are used as tranquillizers, hypnotics, anticonvulsants or muscle relaxants.  Apart from their therapeutic applications, they are often abused by drug addicts and especially in combination with alcohol and other drugs they may lead to severe intoxications. A great number of different benzodiazepines are commercially available and a wide range of therapeutic and toxic concentrations can be present in biological matrices.  

As low-dosed benzodiazepines are difficult to detect with the current screening and chromatographic techniques, a new isolation and chromatographic procedure for low-dosed benzodiazepines has been developed.  After appropriate sample preparation, the final isolation procedure, based on SPE, is applicable to blood and urine samples. The instrumentation used for analysis is a GC-QMS with on-column injection. 

For details on the developed method we refer to the publications section.

(By Daniëlle Borrey)


Opiates

Opiates and their derivatives are very potent analgesics. Commonly used as therapeutic agents, some of these components are also frequently abused as illicit drugs. Although considerable progress has been made in elucidating the mode of action of these drugs, and in the development of analytical techniques to measure morphine, its derivatives and the metabolites, controversy still exists as to the most appropriate method for analyzing these drugs. The main goal of my Ph.D. work is to evaluate the applicability of liquid-chromatography (LC) in opiate analysis.  So far we have demonstrated the use of  LC combined with tandem photo diode array-fluorescence detection and solid-phase extraction for the analysis of opiates in biological fluids1. Furthermore we have applied LC-ion trap mass spectrometry (LC-MS) in the analysis of solid heroin sample, to set up impurity profiles2. At this moment a new LC-MS method combined with simplified sample handling techniques is being developed to identify and quantitate a large variety of drugs of abuse, including opiates, but also cocaine, methadone and their metabolites, in biological fluids, like plasma, urine, saliva, etc.... The method will be applied in a controlled drug study conducted at The National Institute on Drug Abuse (NIDA, NIH, USA) to monitor fetal drug disposition in alternative matrices, after in-utero exposure to methadone, sometimes in combination with cocaine and/ or opiates.

For details on the performed work we refer to the publications section.

(By Riet Dams)


Reported toxicological cases

In an effort to enlarge general toxicological knowledge, intoxications that are seldom described in scientific literature are often reported by the laboratory. Interesting analytical methods have also been pubished (see publications>articles).

Drugs of abuse in saliva:

Mortier K., Maudens K, Lambert W., Clauwaert K., Van Bocxlaer J., Deforce D., Van Peteghem C., De Leenheer A. Simultaneous, quantitative determination of opiates, amphetamines, cocaine and benzoylecgonine in oral fluid by liquid chromatography quadrupole time-of-flight mass spectrometry.  Journal of Chromatography B., 779, 321 (2002).

PMA method:

K.A. Mortier, R. Dams, W.E. Lambert, E.A. De Letter, S. Van Calenbergh, A.P. De Leenheer. Determination of paramethoxyamphetamine and other amphetamine-related designer drugs by liquid chromatography/sonic spray ionization mass spectrometry. Rapid Commun. Mass. Spectrom., 16, 865 (2002). 

Flecainide intoxication:

Analysis of flecainide and two metabolites in biological specimens by HPLC: application to a fatal intoxication. Benijts T, Borrey D, Lambert WE, De Letter EA, Piette MH, Van Peteghem C, De Leenheer AP. J Anal Toxicol 2003 Jan-Feb;27(1):47-52 [Abstract].

Citalopram - moclobemide intoxication:

R. Dams, T.H.P. Benijts, W.E. Lambert, J.F. Van Bocxlaer, D. Van Varenbergh, C. Van Peteghem, and A.P. De Leenheer. A fatal case of serotonin syndrome after combined moclobemide-citalopram intoxication. J. Anal. Toxicol., 25, 147-151 (2001).

Paraquat intoxication:

K. Arys, J. Van Bocxlaer, K. Clauwaert, W. Lambert, M. Piette, C. Van Peteghem and A. De Leenheer. Quantitative determination of paraquat in a fatal intoxication by HPLC-DAD following chemical reduction with sodium borohydride. J. Anal. Toxicol., 24, 116-121 (2000).

Highlighting some benefits of PDA, with examples from real life:

W.E. Lambert, J.F. Van Bocxlaer and A.P. De Leenheer. Potential of high-performance liquid chromatography with photodiode array detection in forensic toxicology. J. Chromatogr. B., 689, 45-53 (1997).

W.E. Lambert, E. Meyer, and A.P. De Leenheer, Systematic toxicological analysis of basic drugs by gradient elution of an alumina-based HPLC packing material under alkaline conditions. J. Anal. Toxicol., 19, 73-78 (1995).