scholarly journals Phase II Metabolism of Asarone Isomers In Vitro and in Humans Using HPLC-MS/MS and HPLC-qToF/MS

Foods ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2032
Author(s):  
Lena Hermes ◽  
Janis Römermann ◽  
Benedikt Cramer ◽  
Melanie Esselen
Keyword(s):  
Mass Spectrometry ◽  
High Pressure ◽  
Liquid Chromatography ◽  
Phase Ii ◽  
High Pressure Liquid Chromatography ◽  
Excretion Rate ◽  
Liver Microsomes ◽  
Oral Intake ◽  
Phase Ii Metabolites

(1) Background: Metabolism data of asarone isomers, in particular phase II, in vitro and in humans is limited so far. For the first time, phase II metabolites of asarone isomers were characterized and human kinetic as well as excretion data after oral intake of asarone-containing tea infusion was determined. (2) Methods: A high pressure liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-qTOF-MS) approach was used to identify phase II metabolites using liver microsomes of different species and in human urine samples. For quantitation of the respective glucuronides, a beta-glucuronidase treatment was performed prior to analysis via high pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). (3) Results: Ingested beta-asarone and erythro and threo-asarone diols were excreted as diols and respective diol glucuronide conjugates within 24 h. An excretion rate about 42% was estimated. O-Demethylation of beta-asarone was also indicated as a human metabolic pathway because a corresponding glucuronic acid conjugate was suggested. (4) Conclusions: Already reported O-demethylation and epoxide-derived diols formation in phase I metabolism of beta-asarone in vitro was verified in humans and glucuronidation was characterized as main conjugation reaction. The excretion rate of 42% as erythro and threo-asarone diols and respective asarone diol glucuronides suggests that epoxide formation is a key step in beta-asarone metabolism, but further, as yet unknown metabolites should also be taken into consideration.

scholarly journals Identification of in vitro and in vivo potential metabolites of novel cardiovascular and adrenolytic drugs by liquid chromatography-mass spectrometry with the aid of experimental design

2019 ◽  
Vol 18 (2) ◽  
pp. 179-194
Author(s):  
Malgorzata Szultka-Mlynska ◽  
Katarzyna Pauter ◽  
Boguslaw Buszewski
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Phase Ii ◽  
Liver Microsomes ◽  
Biologically Active ◽  
Rat Liver Microsomes ◽  
Gas Temperature ◽  
Liquid Chromatography Tandem Mass

Abstract Drug metabolism in liver microsomes was studied in vitro using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Relevant drug was incubated with dog, human and rat liver microsomes (DLMs, HLMs, RLMs) along with NADPH, and the reaction mixture was analyzed by LC-MS/MS to obtain specific metabolic profile. GRACE analytical C18 column, Vision HT (50 × 2 mm, 1.5 μm) was implemented with acetonitrile and water (+ 5 mM ammonium acetate) in a gradient mode as the mobile phase at a flow 0.4 mL.min−1. Different phase I and phase II metabolites were detected and structurally described. The metabolism of the studied drugs occurred via oxidation, hydroxylation and oxidative deamination processes. Conjugates with the glucuronic acid and sulfate were also observed as phase II biotransformation. The central composite design (CCD) showed that factors, such as time incubation, liver microsomal enzymes concentration and NADPH concentration, along with drying gas temperature, nebulizer gas pressure and capillary voltage significantly affected the final response of the method. This study describes the novel information about the chemical structure of the potential metabolites of selected biologically active compounds, which provide vital data for further pharmacokinetic and in vivo metabolism studies.

scholarly journals Fast log P determination by ultra-high-pressure liquid chromatography coupled with UV and mass spectrometry detections

2009 ◽  
Vol 394 (7) ◽  
pp. 1919-1930 ◽  
Author(s):  
Yveline Henchoz ◽  
Davy Guillarme ◽  
Sophie Martel ◽  
Serge Rudaz ◽  
Jean-Luc Veuthey ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Pressure ◽  
Liquid Chromatography ◽  
High Pressure Liquid Chromatography ◽  
Log P ◽  
Ultra High Pressure

Vasopressin is metabolized by a trypsinlike enzyme in guinea pig amniotic fluid

1989 ◽  
Vol 257 (3) ◽  
pp. E354-E360 ◽  
Author(s):  
C. F. Uyehara ◽  
A. K. Sato ◽  
J. R. Claybaugh
Keyword(s):  
High Pressure ◽  
Liquid Chromatography ◽  
Guinea Pig ◽  
Amniotic Fluid ◽  
High Pressure Liquid Chromatography ◽  
Trypsin Inhibitor ◽  
Arginine Vasopressin ◽  
Proteolytic Enzyme

We have demonstrated that arginine vasopressin (AVP) is degraded to desglycinamide AVP by a trypsinlike enzyme found in guinea pig amniotic fluid. Incubation of [3H]AVP with guinea pig amniotic fluid in vivo or in vitro produced a metabolite that comigrated on high-pressure liquid chromatography with desglycinamide AVP in three different buffer systems. Also, AVP antisera that cross-reacted with standard desglycinamide AVP could detect this amniotic fluid metabolite. Because the enzyme responsible for the cleavage of glycinamide from AVP was likely to be trypsin, experiments with aprotinin, a trypsin inhibitor, were conducted. Results demonstrated that the production of the amniotic fluid AVP metabolite could be completely blocked in the presence of the trypsin inhibitor. In addition, examination of amniotic fluid collected from fetuses in the second half of gestation (term = 68 days) showed that AVP could not be metabolized to desglycinamide AVP until after 52 days of gestation. In conclusion, AVP appears to be metabolized by a trypsinlike enzyme in amniotic fluid, and because trypsin is a general proteolytic enzyme, the amniotic compartment may also serve as a clearance site for other proteins.

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