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Papers by Mireille De Doncker
Analytical and bioanalytical chemistry, Jan 9, 2015
Ethyl glucuronide (EtG) is a minor phase II metabolite of alcohol that accumulates in hair. It ha... more Ethyl glucuronide (EtG) is a minor phase II metabolite of alcohol that accumulates in hair. It has been established as a sensitive marker to assess the retrospective consumption of alcohol over recent months using a cut-off of ≥7 pg/mg hair to assess repeated alcohol consumption. The primary aim was to assess whether amounts of alcohol consumed correlated with EtG concentrations in hair. Additionally, we investigated whether the current applied cut-off value of 7 pg/mg hair was adequate to assess the regular consumption of low-to-moderate amounts of alcohol. A prospective controlled alcohol-dosing study in 30 healthy individuals matched on age and gender. Individuals were instructed to drink no alcohol (N = 10), 100 g alcohol per week (N = 10) or 150 g alcohol per week (N = 10) for 12 consecutive weeks, before and after which hair was collected. Throughout the study, compliance to daily alcohol consumption was assessed by analyzing urine EtG three times weekly. Participants in the n...
Forensic Toxicology, 2015
Clinical Biochemistry, 2014
Clozapine is an atypical antipsychotic with a narrow therapeutic range and serious toxic side eff... more Clozapine is an atypical antipsychotic with a narrow therapeutic range and serious toxic side effects. According to AGNP-TDM consensus guidelines, therapeutic drug monitoring (TDM) of clozapine and its metabolite norclozapine is strongly recommended. 330 serum samples, sent to the toxicological laboratory of Ziekenhuis Netwerk Antwerpen for monitoring of clozapine, were tested with a new ultra-high performance liquid chromatography-tandem mass spectrometric method (UHPLC-MS/MS). The aim of this research was to evaluate this method for TDM of clozapine and norclozapine, but also to determine other antipsychotics present in these serum samples. Serum samples were taken just prior to the morning dose of the antipsychotic (trough concentration). All samples were, after a simple liquid-liquid extraction with methyl t-butylether, analyzed using a fully validated UHPLC-MS/MS method which is able to quantitate 16 different antipsychotics and 8 of their major metabolites. Serum concentrations were compared with the therapeutic ranges as defined by the AGNP-TDM guidelines. For clozapine, only 22.3% of the serum concentrations were within the therapeutic range of 350-600 ng/mL, while 67.9% of the concentrations were below 350 ng/mL. For norclozapine, 68.2% of the serum samples were within the therapeutic range of 100-600 ng/mL. The mean clozapine:norclozapine ratio was 1.7 (SD 0.8). 218 of the 330 serum samples contained other antipsychotics than clozapine. Only 52.5% of these concentrations were within the proposed range. This retrospective study highlights the importance of TDM for clozapine and other APs, since many patients show suboptimal serum concentrations.
Forensic Science International, 2015
Therapeutic Drug Monitoring, 2005
Forensic Science International, 2010
Drug and Alcohol Dependence, 2014
Clinical Toxicology, 2008
Cibenzoline is an antiarrhythmic drug used to treat patients with supraventricular or ventricular... more Cibenzoline is an antiarrhythmic drug used to treat patients with supraventricular or ventricular arrhythmias. Cibenzoline overdose is associated with proarrhythmic and hemodynamic effects such as hypotension and congestive heart failure. We report a case of cardiogenic shock due to cibenzoline overdose in a patient with progressive renal insufficiency. The standard treatment of a cibenzoline intoxication is symptomatic, but we used combined hemoperfusion-hemodialysis to treat our patient. This was associated with a rapid decline in plasma cibenzoline concentration and improvement of the clinical condition. However, only 28.98 mg of an estimated body pool of cibenzoline (447.2 to 806.6 mg) was removed during the 8 hours of treatment.
Clinical Chemistry and Laboratory Medicine, 2000
Clinica Chimica Acta, 2014
Therapeutic drug monitoring of antipsychotics is important for optimizing therapy, explaining adv... more Therapeutic drug monitoring of antipsychotics is important for optimizing therapy, explaining adverse effects, non-response or poor compliance. We developed a UHPLC-MS/MS method for quantification of 16 commonly used and recently marketed antipsychotics and 8 metabolites in serum. After liquid-liquid extraction using methyl tert-butyl ether, analysis was performed on an Agilent Technologies 1290 Infinity LC system coupled with an Agilent Technologies 6460 Triple Quadrupole MS. Separation with a C18 column and gradient elution at 0.5 mL/min resulted in a 6-min run-time. Detection was performed in dynamic MRM, monitoring 3 ion transitions per compound. Isotope labeled internal standards were used for every compound, except for bromperidol and levosulpiride. Mean recovery was 86.8%. Matrix effects were -18.4 to +9.1%. Accuracy ranged between 91.3 and 107.0% at low, medium and high concentrations and between 76.2 and 113.9% at LLOQ. Within-run precision was <15% (CV), except for asenapine and hydroxy-iloperidone. Between-run precision was aberrant only for 7-hydroxy-N-desalkylquetiapine, asenapine and reduced haloperidol. No interferences were found. No problems of instability were observed, even for olanzapine. The method was successfully applied on patient samples. The liquid-liquid extraction and UHPLC-MS/MS technique allows robust target screening and quantification of 23 antipsychotics and metabolites.
Clinica Chimica Acta, 2013
Analytical and bioanalytical chemistry, Jan 9, 2015
Ethyl glucuronide (EtG) is a minor phase II metabolite of alcohol that accumulates in hair. It ha... more Ethyl glucuronide (EtG) is a minor phase II metabolite of alcohol that accumulates in hair. It has been established as a sensitive marker to assess the retrospective consumption of alcohol over recent months using a cut-off of ≥7 pg/mg hair to assess repeated alcohol consumption. The primary aim was to assess whether amounts of alcohol consumed correlated with EtG concentrations in hair. Additionally, we investigated whether the current applied cut-off value of 7 pg/mg hair was adequate to assess the regular consumption of low-to-moderate amounts of alcohol. A prospective controlled alcohol-dosing study in 30 healthy individuals matched on age and gender. Individuals were instructed to drink no alcohol (N = 10), 100 g alcohol per week (N = 10) or 150 g alcohol per week (N = 10) for 12 consecutive weeks, before and after which hair was collected. Throughout the study, compliance to daily alcohol consumption was assessed by analyzing urine EtG three times weekly. Participants in the n...
Forensic Toxicology, 2015
Clinical Biochemistry, 2014
Clozapine is an atypical antipsychotic with a narrow therapeutic range and serious toxic side eff... more Clozapine is an atypical antipsychotic with a narrow therapeutic range and serious toxic side effects. According to AGNP-TDM consensus guidelines, therapeutic drug monitoring (TDM) of clozapine and its metabolite norclozapine is strongly recommended. 330 serum samples, sent to the toxicological laboratory of Ziekenhuis Netwerk Antwerpen for monitoring of clozapine, were tested with a new ultra-high performance liquid chromatography-tandem mass spectrometric method (UHPLC-MS/MS). The aim of this research was to evaluate this method for TDM of clozapine and norclozapine, but also to determine other antipsychotics present in these serum samples. Serum samples were taken just prior to the morning dose of the antipsychotic (trough concentration). All samples were, after a simple liquid-liquid extraction with methyl t-butylether, analyzed using a fully validated UHPLC-MS/MS method which is able to quantitate 16 different antipsychotics and 8 of their major metabolites. Serum concentrations were compared with the therapeutic ranges as defined by the AGNP-TDM guidelines. For clozapine, only 22.3% of the serum concentrations were within the therapeutic range of 350-600 ng/mL, while 67.9% of the concentrations were below 350 ng/mL. For norclozapine, 68.2% of the serum samples were within the therapeutic range of 100-600 ng/mL. The mean clozapine:norclozapine ratio was 1.7 (SD 0.8). 218 of the 330 serum samples contained other antipsychotics than clozapine. Only 52.5% of these concentrations were within the proposed range. This retrospective study highlights the importance of TDM for clozapine and other APs, since many patients show suboptimal serum concentrations.
Forensic Science International, 2015
Therapeutic Drug Monitoring, 2005
Forensic Science International, 2010
Drug and Alcohol Dependence, 2014
Clinical Toxicology, 2008
Cibenzoline is an antiarrhythmic drug used to treat patients with supraventricular or ventricular... more Cibenzoline is an antiarrhythmic drug used to treat patients with supraventricular or ventricular arrhythmias. Cibenzoline overdose is associated with proarrhythmic and hemodynamic effects such as hypotension and congestive heart failure. We report a case of cardiogenic shock due to cibenzoline overdose in a patient with progressive renal insufficiency. The standard treatment of a cibenzoline intoxication is symptomatic, but we used combined hemoperfusion-hemodialysis to treat our patient. This was associated with a rapid decline in plasma cibenzoline concentration and improvement of the clinical condition. However, only 28.98 mg of an estimated body pool of cibenzoline (447.2 to 806.6 mg) was removed during the 8 hours of treatment.
Clinical Chemistry and Laboratory Medicine, 2000
Clinica Chimica Acta, 2014
Therapeutic drug monitoring of antipsychotics is important for optimizing therapy, explaining adv... more Therapeutic drug monitoring of antipsychotics is important for optimizing therapy, explaining adverse effects, non-response or poor compliance. We developed a UHPLC-MS/MS method for quantification of 16 commonly used and recently marketed antipsychotics and 8 metabolites in serum. After liquid-liquid extraction using methyl tert-butyl ether, analysis was performed on an Agilent Technologies 1290 Infinity LC system coupled with an Agilent Technologies 6460 Triple Quadrupole MS. Separation with a C18 column and gradient elution at 0.5 mL/min resulted in a 6-min run-time. Detection was performed in dynamic MRM, monitoring 3 ion transitions per compound. Isotope labeled internal standards were used for every compound, except for bromperidol and levosulpiride. Mean recovery was 86.8%. Matrix effects were -18.4 to +9.1%. Accuracy ranged between 91.3 and 107.0% at low, medium and high concentrations and between 76.2 and 113.9% at LLOQ. Within-run precision was <15% (CV), except for asenapine and hydroxy-iloperidone. Between-run precision was aberrant only for 7-hydroxy-N-desalkylquetiapine, asenapine and reduced haloperidol. No interferences were found. No problems of instability were observed, even for olanzapine. The method was successfully applied on patient samples. The liquid-liquid extraction and UHPLC-MS/MS technique allows robust target screening and quantification of 23 antipsychotics and metabolites.
Clinica Chimica Acta, 2013