Gas Chromatography - Mass Spectrometry Designation and Prediction of Metabolic Dealkylation and Hydroxylation Reactions in Xenobiotics

Enzymatic disproportionation of cyclohex-2-enone was screened using Agilent J&W GC columns. Published by Elsevier B. V. Essential oils of six Juniperus taxa indigenous in Greece Parasitology Research, 110, 1829-1839 (2012) Tags F. Vourlioti-Arapi et al. HP-5ms, 7890A GC, 5957C MSD, clinical research, disease research Abstract Juniper essential oils were analyzed on an Agilent J&W HP-5ms column in an Agilent 7890A/5957C GC/MS. Published by Springer.Juniper essential oils were analyzed on an Agilent J&W HP-5ms column in an Agilent 7890A/5957C GC/MS. Published by Springer. Gas Chromatography-Mass Spectrometry Designation and Prediction of Metabolic Dealkylation and Hydroxylation Reactions in Xenobiotics Exemplified by Tramadol Journal of Analytical Toxicology, 33, 34-40 (2009) Tags Babiker M. El-Haj, Abdelkader M. Al-Amri, Heyam S. Ali HP-5ms, clinical research Abstract Metabolic dealkylation and hydroxylation reactions in xenobiotics are common and may take place at different sites in the molecules. Sometimes confusion may arise as to the nature and site of the resulting metabolic change when there is more than one potential site. The use of GC-MS in resolving the problem has been demonstrated by using tramadol as example. Human urine samples containing tramadol and its metabolites were extracted under basic pH conditions and analyzed by GC-MS, in the electron impact and chemical ionization modes, before and after trimethylsilyl (TMS) derivatization. By recognizing the mass-to-charge ratios of molecular and base-peak ions in the mass spectra, it was possible to predict and designate sites of demethylation and hydroxylation in tramadol metabolites. In addition to the designation of the known tramadol metabolites, the practice has led to the tentative characterization of hydroxytramadol and norhydroxytramadol as new metabolites of tramadol in humans. Possible extension of the modus operandi to other xenobiotics was discussed. © Oxford University Press reserved/ not to be reused or distributed without the prior written permission of the Publishers.Metabolic dealkylation and hydroxylation reactions in xenobiotics are common and may take place at different sites in the molecules. Sometimes confusion may arise as to the nature and site of the resulting metabolic change when there is more than one potential site. The use of GC-MS in resolving the problem has been demonstrated by using tramadol as example. Human urine samples containing tramadol and its metabolites were extracted under basic pH conditions and analyzed by GC-MS, in the electron impact and chemical ionization modes, before and after trimethylsilyl (TMS) derivatization. By recognizing the mass-to-charge ratios of molecular and base-peak ions in the mass spectra, it was possible to predict and designate sites of demethylation and hydroxylation in tramadol metabolites. In addition to the designation of the known tramadol metabolites, the practice has led to the tentative characterization of hydroxytramadol and norhydroxytramadol as new metabolites of tramadol in humans. Possible extension of the modus operandi to other xenobiotics was discussed. © Oxford University Press reserved/ not to be reused or distributed without the prior written permission of the Publishers. Buprenorphine Alters Desmethylflunitrazepam Disposition and Flunitrazepam Toxicity in Rats Toxicological Sciences, 106, 64-73 (2008) Tags S. Pirnay et al. HP-5ms, clinical research Abstract High-dosage buprenorphine (BUP) consumed concomitantly with benzodiazepines (BZDs) including flunitrazepam (FZ) may cause life-threatening respiratory depression despite a BUP ceiling effect and BZDs’ limited effects on ventilation. However, the mechanism of BUP/FZ interaction remains unknown. We hypothesized that BUP may alter the disposition of FZ active metabolites in vivo, contributing to respiratory toxicity. Plasma FZ, desmethylflunitrazepam (DMFZ), and 7aminoflunitrazepam (7-AFZ) concentrations were measured using gas chromatography–mass spectrometry. Intravenous BUP 30 mg/kg pretreatment did not alter plasma FZ and 7-AFZ kinetics in Sprague-Dawley rats infused with 40 mg/kg FZ over 30 min, whereas resulting in a three-fold increase in the area under the curve (AUC) of DMFZ concentrations compared with control (p < 0.01). In contrast, BUP did not significantly modify plasma DMFZ concentrations after intravenous infusion of 7 mg/kg DMFZ, whereas resulting in a similar peak concentration to that generated from 40 mg/kg FZ administration. Regarding the effects on ventilation, BUP (30 mg/kg) as well as its combination with FZ (0.3 mg/kg) significantly increased PaCO2, whereas only BUP/FZ combination decreased PaO2 (p < 0.001). Interestingly, FZ (40 mg/kg) but not DMFZ (40 mg/kg) significantly increased PaCO2 (p < 0.05), whereas DMFZ but not FZ decreased PaO2 (p < 0.05). Thus, decrease in PaO2 appears related to BUP-mediated effects on DMFZ disposition, although increases in PaCO2 relate to direct BUP/FZ additive or synergistic dynamic interactions. We conclude that combined high-dosage BUP and FZ is responsible for increased respiratory toxicity in which BUP-mediated alteration in DMFZ disposition may play a significant role. © Oxford University Press reserved/ not to be reused or distributed without the prior written permission of the Publishers.High-dosage buprenorphine (BUP) consumed concomitantly with benzodiazepines (BZDs) including flunitrazepam (FZ) may cause life-threatening respiratory depression despite a BUP ceiling effect and BZDs’ limited effects on ventilation. However, the mechanism of BUP/FZ interaction remains unknown. We hypothesized that BUP may alter the disposition of FZ active metabolites in vivo, contributing to respiratory toxicity. Plasma FZ, desmethylflunitrazepam (DMFZ), and 7aminoflunitrazepam (7-AFZ) concentrations were measured using gas chromatography–mass spectrometry. Intravenous BUP 30 mg/kg pretreatment did not alter plasma FZ and 7-AFZ kinetics in Sprague-Dawley rats infused with 40 mg/kg FZ over 30 min, whereas resulting in a three-fold increase in the area under the curve (AUC) of DMFZ concentrations compared with control (p < 0.01). In contrast, BUP did not significantly modify plasma DMFZ concentrations after intravenous infusion of 7 mg/kg DMFZ, whereas resulting in a similar peak concentration to that generated from 40 mg/kg FZ administration. Regarding the effects on ventilation, BUP (30 mg/kg) as well as its combination with FZ (0.3 mg/kg) significantly increased PaCO2, whereas only BUP/FZ combination decreased PaO2 (p < 0.001). Interestingly, FZ (40 mg/kg) but not DMFZ (40 mg/kg) significantly increased PaCO2 (p < 0.05), whereas DMFZ but not FZ decreased PaO2 (p < 0.05). Thus, decrease in PaO2 appears related to BUP-mediated effects on DMFZ disposition, although increases in PaCO2 relate to direct BUP/FZ additive or synergistic dynamic interactions. We conclude that combined high-dosage BUP and FZ is responsible for increased respiratory toxicity in which BUP-mediated alteration in DMFZ disposition may play a significant role. © Oxford University Press reserved/ not to be reused or distributed without the prior written permission of the Publishers.