A headspace-trap gas chromatography-mass spectrometry (HS-trap GC-MS) method was developed to det... more A headspace-trap gas chromatography-mass spectrometry (HS-trap GC-MS) method was developed to determine GHB, a low molecular weight compound and drug of abuse, in various biological fluids. Combining this relatively novel and fully automated headspace technique with "in-vial" methylation of GHB allowed for a straightforward approach. One single method could be used for all biofluids (urine, plasma, serum, whole blood or lyzed blood), requiring only 100 µl of sample. Moreover, our approach involves mere addition of all reagents and sample into one vial. Following optimization of headspace conditions and trap settings, validation was performed. Although sample preparation only consists of the addition of salt and derivatization reagents directly to a 100 µl-sample in a HS-vial, adequate method sensitivity and selectivity was obtained. Calibration curves ranged from 5 to 150 µg/ml GHB for urine, from 2 to 150 µg/ml for plasma, and from 3.5 to 200 µg/ml for whole blood. Acceptable precision and accuracy (<13 % bias and imprecision) was seen for all quality controls (QC's) (LLOQ-level, low, medium, high), including for the supplementary serum-and lyzed blood-based QC's, using calibration curves prepared in plasma or whole blood, respectively. Incurred sample reanalysis demonstrated assay reproducibility, while cross-validation with another GC-MS method demonstrated that our method is a valuable alternative for GHB determination in toxicological samples, with the advantage of requiring only 100 µl and minimal hands-on time, as sample preparation is easy and injection automated. Gamma-hydroxybutyric acid (GHB), in-vial derivatization, gas chromatography coupled to mass spectrometry (GC-MS), headspace-trap (HS-trap), biological matrices, toxicology
Objectives Fast and reliable ethanol assays analysis are used in a clinical context for patients ... more Objectives Fast and reliable ethanol assays analysis are used in a clinical context for patients suspected of ethanol intoxication. Mostly, automated systems using an enzymatic reaction based on ethanol dehydrogenase are used. The manuscript focusses on the evaluation of the performance of these assays. Methods Data included 30 serum samples used in the Belgian EQA scheme from 2019 to 2021 and concentrations ranged from 0.13 to 3.70 g/L. A regression line between target concentrations and reported values was calculated to evaluate outliers, bias, variability and measurement uncertainty. Results A total of 1,611 results were taken into account. Bias was the highest for Alinity c over the whole concentration range and the lowest for Vitros for low concentrations and Cobas 8000 using the c702 module for high concentrations. The Architect and Cobas c501/c502 systems showed the lowest variability over the whole concentration range. Highest variability was observed for Cobas 8000 using th...
Guanabara Bay (Rio de Janeiro State, Southeast Brazilian region) is the most anthropogenically di... more Guanabara Bay (Rio de Janeiro State, Southeast Brazilian region) is the most anthropogenically disturbed area along the lengthy (around 8500 km) Brazilian coastline. The estuary is bordered by 12000 industries and four cities (including Rio de Janeiro metropolitan area) with a total population of about 11 million people 2. Despite the anthropogenic pressure, Guanabara Bay supplies food and breeding grounds for marine tucuxi dolphins (Sotalia guianensis). This dolphin species occurs exclusively in coastal ...
... Maes, M.; Song, C.; Lin, A.; Jongh, de, R.; Gastel, van, A.; Kenis, G.; Bosmans, E.; Meester,... more ... Maes, M.; Song, C.; Lin, A.; Jongh, de, R.; Gastel, van, A.; Kenis, G.; Bosmans, E.; Meester, De, Ingrid; Neels, Hugo; Janca, A.; Scharpé, Simon; Smith, R. - Immune and clinical correlates of psychological stress-induced production of interferon-γ and interleukin-10 in humans - In ...
Since Belgian law recently set a limit to morphine concentration detectable in blood and urine wh... more Since Belgian law recently set a limit to morphine concentration detectable in blood and urine while driving a vehicle, questions arose about the implications for the medical use of opiates. We determined morphine concentrations in whole blood and urine by gas chromatography±mass spectrometry in 15 patients on continuous intrathecal morphine administration. Effects on blood and urine concentration after water intake and the correlation with the intrathecal morphine daily dose were also evaluated. Our results confirm that, in all patients examined, the legally determined maximum blood morphine concentration of 20 ng/ml was never exceeded. Even patients on high intrathecal morphine dose schedules did never reach the maximum legal blood concentration. However, morphine concentration in urine reached levels which exceeded by far the legally determined maximum concentration of 300 ng/ml. Although legal actions against driving under the influence of morphine can only be taken after a positive urine and a subsequent positive blood sample, drivers on intrathecal opiates must be aware of the possibility of a positive roadside drug test.
Toxicological data on overdose with HIV-inhibitors is scarce. We present a case report of two ind... more Toxicological data on overdose with HIV-inhibitors is scarce. We present a case report of two independent suicide attempts by self-administered overdose with the same antiretroviral medicine Genvoya® (emtricitabine/elvitegravir/tenofovir alafenamide/cobicistat). Both patients were admitted to the hospital and presented with a loss of consciousness, lactic acidosis, elevated hepatic transaminase levels and hemodynamic instability. While one patient survived with advanced supportive measures, the other passed away. Emtricitabine levels were measured in vivo in various consecutive serum samples and post-mortem urine, peripheral and cardiac serum samples and confirmed excessive use in both cases. This is the first time emtricitabine levels following overdose are reported. Although measured concentrations for emtricitabine were quite similar in these cases, metabolic acidosis was more pronounced in the fatal case. The difference in outcome between the two could be due to a difference in physiological status, susceptibility to accumulation and adverse effects, and perhaps a varying interval between ingestion and the start of supportive measures.
Monitoring long‐term alcohol use and/or abstinence is essential in clinical and medico‐legal case... more Monitoring long‐term alcohol use and/or abstinence is essential in clinical and medico‐legal cases. Analysis of ethyl glucuronide (EtG) in hair provides information on alcohol consumption over several months. However, there is a lag time between ethanol consumption, incorporation of EtG in the hair bulb and hair growing out of the scalp. Phosphatidylethanol (PEth) 16:0/18:1 analysis in whole blood has a detection window of 2–4 weeks, allowing for the detection of recent alcohol consumption. In this study, 2340 paired samples (of hair and venous whole blood from 1170 individuals) were analysed for EtG in hair (hEtG) and PEth 16:0/18:1 in venous whole blood. PEth 16:0/18:1 and hEtG results were subdivided into three categories according to the consensus of SoHT (hEtG) and PEth‐NET (PEth): abstinence/low, moderate or excessive alcohol consumption. For hEtG analysis, 446 individuals presented abstinence/low alcohol consumption, of which 2% were classified as excessive alcohol users through PEth 16:0/18:1 analysis. This suggests excessive alcohol consumption in the weeks before sample collection. Out of 483 individuals classified as heavy alcohol users based on hEtG analysis, 14% showed abstinence/low alcohol consumption for PEth 16:0/18:1 analysis, implying that these subjects stopped drinking 2–4 weeks before sample collection. Our results show that the analysis of the two different biomarkers can lead to a more accurate categorisation of individuals. Therefore, we emphasize that for the retrospective investigation of alcohol use, it is necessary to include two alcohol use biomarkers with different detection windows.
... LN van Nuijs a , Corresponding Author Contact Information , E-mail The Corresponding Author ,... more ... LN van Nuijs a , Corresponding Author Contact Information , E-mail The Corresponding Author ,Bert Pecceu b , E ... Each river site was sampled twice, during the summer of 2007 and the winter of 2007 ... Grab samples (2.5 L) were collected from 10 sites on 6 rivers and brooks in ...
A 22-year-old man was hospitalized after stating he would ‘commit suicide in a non-detectable way... more A 22-year-old man was hospitalized after stating he would ‘commit suicide in a non-detectable way’. He was admitted with a severe necrotizing pancreatitis and acute kidney injury, evolving to multiple organ failure. His condition rapidly deteriorated, and he died 11 days after hospital admission. Postmortem histopathology confirmed fulminant necrotizing pancreatitis, acute tubular necrosis, cerebral edema, pericentral/midzonal hepatocellular necrosis and acute respiratory distress syndrome. Metabolites of 4F-MDMB-BINACA, a synthetic cannabinoid, were detected in urine and serum collected at hospital admission. The same drug was found in a vapor fluid found in the man’s apartment. As cannabis use has been etiologically linked to acute pancreatitis, we hypothesize that the more afferent and potent 4F-MDMB-BINACA could induce acute pancreatitis via stimulation of cannabinoid (CB)1-receptors. Alternatively, terminal fluorination could have induced a dose-dependent toxic effect on a wide range of cellular processes, leading to cell dysfunction and death. This is the first clinicopathological description of a lethal intoxication with 4F-MDMB-BINACA, following extensive vaping. Toxic effects could either relate to CB-receptor binding or to direct fluoride toxicity.
Expert Opinion on Drug Metabolism & Toxicology, 2018
Introduction Bipolar disorder is a severe, chronic psychiatric disorder with a need for long-term... more Introduction Bipolar disorder is a severe, chronic psychiatric disorder with a need for long-term treatment. Patient non-adherence is frequent and poses a major problem in maintenance therapy. Aripiprazole once-monthly long-acting injectable (AOM LAI) is a recently FDA approved treatment option for maintenance therapy that could be of great value. Areas covered This paper reviews the pharmacokinetic, efficacy and safety data for AOM LAI in bipolar disorder. Expert opinion AOM LAI is a safe and efficacious treatment option in the maintenance therapy of bipolar I disorder. However, further research is still needed to determine the position of AOM LAI relative to other available treatment options.
A patient intentionally ingested an unknown amount of methanol and was admitted to the hospital 6... more A patient intentionally ingested an unknown amount of methanol and was admitted to the hospital 6 h later. On admission, the methanol concentration in blood was estimated as approximately of 134 mmol/L, based on the calculation of the osmolal gap. Intravenous ethanol administration and hemodialysis were promptly started. During hemodialysis, several blood samples were collected for determination of methanol and ethanol concentrations. Initially, we used gas chromatography with split-mode injection of pretreated serum samples; however, methanol concentrations turned out to be significantly lower than expected, based on calculated osmolal gap values. Because no explanation for the excess serum osmolal gap was apparent, we reanalyzed samples, using head-space gas chromatography. The methanol concentrations measured were significantly higher and osmolal gap values were no longer excessive.
The components of biological variation in serum vitamin E in relation to serum cholesterol, trigl... more The components of biological variation in serum vitamin E in relation to serum cholesterol, triglycerides, high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), apolipoprotein A-I (apo A-I), and apo B were examined in 26 healthy volunteers who had monthly blood samplings during one calendar year. The estimated CVs for vitamin E were: interindividual, 19.9%, and intraindividual, 11.9%; the index of individuality (I-index) was 0.59. The I-indices for all lipid variables were < 0.51. Serum concentrations of vitamin E, cholesterol, triglycerides, HDL-C, LDL-C, and apo B were lower in spring than in the other seasons. The peak-trough differences in the yearly variations, expressed as a percentage of the mean, were for vitamin E 14.5%, cholesterol 16.2%, triglycerides 14.5%, and LDL-C 24.3%. A significant common annual rhythm was expressed in vitamin E or lipid variables and in the changes in ambient temperature the weeks before blood sampling (inverse relations). There were hi...
A headspace-trap gas chromatography-mass spectrometry (HS-trap GC-MS) method was developed to det... more A headspace-trap gas chromatography-mass spectrometry (HS-trap GC-MS) method was developed to determine GHB, a low molecular weight compound and drug of abuse, in various biological fluids. Combining this relatively novel and fully automated headspace technique with "in-vial" methylation of GHB allowed for a straightforward approach. One single method could be used for all biofluids (urine, plasma, serum, whole blood or lyzed blood), requiring only 100 µl of sample. Moreover, our approach involves mere addition of all reagents and sample into one vial. Following optimization of headspace conditions and trap settings, validation was performed. Although sample preparation only consists of the addition of salt and derivatization reagents directly to a 100 µl-sample in a HS-vial, adequate method sensitivity and selectivity was obtained. Calibration curves ranged from 5 to 150 µg/ml GHB for urine, from 2 to 150 µg/ml for plasma, and from 3.5 to 200 µg/ml for whole blood. Acceptable precision and accuracy (<13 % bias and imprecision) was seen for all quality controls (QC's) (LLOQ-level, low, medium, high), including for the supplementary serum-and lyzed blood-based QC's, using calibration curves prepared in plasma or whole blood, respectively. Incurred sample reanalysis demonstrated assay reproducibility, while cross-validation with another GC-MS method demonstrated that our method is a valuable alternative for GHB determination in toxicological samples, with the advantage of requiring only 100 µl and minimal hands-on time, as sample preparation is easy and injection automated. Gamma-hydroxybutyric acid (GHB), in-vial derivatization, gas chromatography coupled to mass spectrometry (GC-MS), headspace-trap (HS-trap), biological matrices, toxicology
Objectives Fast and reliable ethanol assays analysis are used in a clinical context for patients ... more Objectives Fast and reliable ethanol assays analysis are used in a clinical context for patients suspected of ethanol intoxication. Mostly, automated systems using an enzymatic reaction based on ethanol dehydrogenase are used. The manuscript focusses on the evaluation of the performance of these assays. Methods Data included 30 serum samples used in the Belgian EQA scheme from 2019 to 2021 and concentrations ranged from 0.13 to 3.70 g/L. A regression line between target concentrations and reported values was calculated to evaluate outliers, bias, variability and measurement uncertainty. Results A total of 1,611 results were taken into account. Bias was the highest for Alinity c over the whole concentration range and the lowest for Vitros for low concentrations and Cobas 8000 using the c702 module for high concentrations. The Architect and Cobas c501/c502 systems showed the lowest variability over the whole concentration range. Highest variability was observed for Cobas 8000 using th...
Guanabara Bay (Rio de Janeiro State, Southeast Brazilian region) is the most anthropogenically di... more Guanabara Bay (Rio de Janeiro State, Southeast Brazilian region) is the most anthropogenically disturbed area along the lengthy (around 8500 km) Brazilian coastline. The estuary is bordered by 12000 industries and four cities (including Rio de Janeiro metropolitan area) with a total population of about 11 million people 2. Despite the anthropogenic pressure, Guanabara Bay supplies food and breeding grounds for marine tucuxi dolphins (Sotalia guianensis). This dolphin species occurs exclusively in coastal ...
... Maes, M.; Song, C.; Lin, A.; Jongh, de, R.; Gastel, van, A.; Kenis, G.; Bosmans, E.; Meester,... more ... Maes, M.; Song, C.; Lin, A.; Jongh, de, R.; Gastel, van, A.; Kenis, G.; Bosmans, E.; Meester, De, Ingrid; Neels, Hugo; Janca, A.; Scharpé, Simon; Smith, R. - Immune and clinical correlates of psychological stress-induced production of interferon-γ and interleukin-10 in humans - In ...
Since Belgian law recently set a limit to morphine concentration detectable in blood and urine wh... more Since Belgian law recently set a limit to morphine concentration detectable in blood and urine while driving a vehicle, questions arose about the implications for the medical use of opiates. We determined morphine concentrations in whole blood and urine by gas chromatography±mass spectrometry in 15 patients on continuous intrathecal morphine administration. Effects on blood and urine concentration after water intake and the correlation with the intrathecal morphine daily dose were also evaluated. Our results confirm that, in all patients examined, the legally determined maximum blood morphine concentration of 20 ng/ml was never exceeded. Even patients on high intrathecal morphine dose schedules did never reach the maximum legal blood concentration. However, morphine concentration in urine reached levels which exceeded by far the legally determined maximum concentration of 300 ng/ml. Although legal actions against driving under the influence of morphine can only be taken after a positive urine and a subsequent positive blood sample, drivers on intrathecal opiates must be aware of the possibility of a positive roadside drug test.
Toxicological data on overdose with HIV-inhibitors is scarce. We present a case report of two ind... more Toxicological data on overdose with HIV-inhibitors is scarce. We present a case report of two independent suicide attempts by self-administered overdose with the same antiretroviral medicine Genvoya® (emtricitabine/elvitegravir/tenofovir alafenamide/cobicistat). Both patients were admitted to the hospital and presented with a loss of consciousness, lactic acidosis, elevated hepatic transaminase levels and hemodynamic instability. While one patient survived with advanced supportive measures, the other passed away. Emtricitabine levels were measured in vivo in various consecutive serum samples and post-mortem urine, peripheral and cardiac serum samples and confirmed excessive use in both cases. This is the first time emtricitabine levels following overdose are reported. Although measured concentrations for emtricitabine were quite similar in these cases, metabolic acidosis was more pronounced in the fatal case. The difference in outcome between the two could be due to a difference in physiological status, susceptibility to accumulation and adverse effects, and perhaps a varying interval between ingestion and the start of supportive measures.
Monitoring long‐term alcohol use and/or abstinence is essential in clinical and medico‐legal case... more Monitoring long‐term alcohol use and/or abstinence is essential in clinical and medico‐legal cases. Analysis of ethyl glucuronide (EtG) in hair provides information on alcohol consumption over several months. However, there is a lag time between ethanol consumption, incorporation of EtG in the hair bulb and hair growing out of the scalp. Phosphatidylethanol (PEth) 16:0/18:1 analysis in whole blood has a detection window of 2–4 weeks, allowing for the detection of recent alcohol consumption. In this study, 2340 paired samples (of hair and venous whole blood from 1170 individuals) were analysed for EtG in hair (hEtG) and PEth 16:0/18:1 in venous whole blood. PEth 16:0/18:1 and hEtG results were subdivided into three categories according to the consensus of SoHT (hEtG) and PEth‐NET (PEth): abstinence/low, moderate or excessive alcohol consumption. For hEtG analysis, 446 individuals presented abstinence/low alcohol consumption, of which 2% were classified as excessive alcohol users through PEth 16:0/18:1 analysis. This suggests excessive alcohol consumption in the weeks before sample collection. Out of 483 individuals classified as heavy alcohol users based on hEtG analysis, 14% showed abstinence/low alcohol consumption for PEth 16:0/18:1 analysis, implying that these subjects stopped drinking 2–4 weeks before sample collection. Our results show that the analysis of the two different biomarkers can lead to a more accurate categorisation of individuals. Therefore, we emphasize that for the retrospective investigation of alcohol use, it is necessary to include two alcohol use biomarkers with different detection windows.
... LN van Nuijs a , Corresponding Author Contact Information , E-mail The Corresponding Author ,... more ... LN van Nuijs a , Corresponding Author Contact Information , E-mail The Corresponding Author ,Bert Pecceu b , E ... Each river site was sampled twice, during the summer of 2007 and the winter of 2007 ... Grab samples (2.5 L) were collected from 10 sites on 6 rivers and brooks in ...
A 22-year-old man was hospitalized after stating he would ‘commit suicide in a non-detectable way... more A 22-year-old man was hospitalized after stating he would ‘commit suicide in a non-detectable way’. He was admitted with a severe necrotizing pancreatitis and acute kidney injury, evolving to multiple organ failure. His condition rapidly deteriorated, and he died 11 days after hospital admission. Postmortem histopathology confirmed fulminant necrotizing pancreatitis, acute tubular necrosis, cerebral edema, pericentral/midzonal hepatocellular necrosis and acute respiratory distress syndrome. Metabolites of 4F-MDMB-BINACA, a synthetic cannabinoid, were detected in urine and serum collected at hospital admission. The same drug was found in a vapor fluid found in the man’s apartment. As cannabis use has been etiologically linked to acute pancreatitis, we hypothesize that the more afferent and potent 4F-MDMB-BINACA could induce acute pancreatitis via stimulation of cannabinoid (CB)1-receptors. Alternatively, terminal fluorination could have induced a dose-dependent toxic effect on a wide range of cellular processes, leading to cell dysfunction and death. This is the first clinicopathological description of a lethal intoxication with 4F-MDMB-BINACA, following extensive vaping. Toxic effects could either relate to CB-receptor binding or to direct fluoride toxicity.
Expert Opinion on Drug Metabolism & Toxicology, 2018
Introduction Bipolar disorder is a severe, chronic psychiatric disorder with a need for long-term... more Introduction Bipolar disorder is a severe, chronic psychiatric disorder with a need for long-term treatment. Patient non-adherence is frequent and poses a major problem in maintenance therapy. Aripiprazole once-monthly long-acting injectable (AOM LAI) is a recently FDA approved treatment option for maintenance therapy that could be of great value. Areas covered This paper reviews the pharmacokinetic, efficacy and safety data for AOM LAI in bipolar disorder. Expert opinion AOM LAI is a safe and efficacious treatment option in the maintenance therapy of bipolar I disorder. However, further research is still needed to determine the position of AOM LAI relative to other available treatment options.
A patient intentionally ingested an unknown amount of methanol and was admitted to the hospital 6... more A patient intentionally ingested an unknown amount of methanol and was admitted to the hospital 6 h later. On admission, the methanol concentration in blood was estimated as approximately of 134 mmol/L, based on the calculation of the osmolal gap. Intravenous ethanol administration and hemodialysis were promptly started. During hemodialysis, several blood samples were collected for determination of methanol and ethanol concentrations. Initially, we used gas chromatography with split-mode injection of pretreated serum samples; however, methanol concentrations turned out to be significantly lower than expected, based on calculated osmolal gap values. Because no explanation for the excess serum osmolal gap was apparent, we reanalyzed samples, using head-space gas chromatography. The methanol concentrations measured were significantly higher and osmolal gap values were no longer excessive.
The components of biological variation in serum vitamin E in relation to serum cholesterol, trigl... more The components of biological variation in serum vitamin E in relation to serum cholesterol, triglycerides, high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), apolipoprotein A-I (apo A-I), and apo B were examined in 26 healthy volunteers who had monthly blood samplings during one calendar year. The estimated CVs for vitamin E were: interindividual, 19.9%, and intraindividual, 11.9%; the index of individuality (I-index) was 0.59. The I-indices for all lipid variables were < 0.51. Serum concentrations of vitamin E, cholesterol, triglycerides, HDL-C, LDL-C, and apo B were lower in spring than in the other seasons. The peak-trough differences in the yearly variations, expressed as a percentage of the mean, were for vitamin E 14.5%, cholesterol 16.2%, triglycerides 14.5%, and LDL-C 24.3%. A significant common annual rhythm was expressed in vitamin E or lipid variables and in the changes in ambient temperature the weeks before blood sampling (inverse relations). There were hi...
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