scholarly journals Metabolites of Medicarpin and Their Distributions in Rats

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1966 ◽  
Author(s):  
Hong-Yan Wang ◽  
Teng Li ◽  
Rui Ji ◽  
Feng Xu ◽  
Guang-Xue Liu ◽  
...  
Keyword(s):  
Vitamin C ◽  
Oral Administration ◽  
Phase I ◽  
Metabolic Fate ◽  
Detailed Report ◽  
Metabolic Reactions ◽  
Phase Ii Metabolites ◽  
New Compounds ◽  
New Metabolites

Medicarpin is a bioactive pterocarpan that has been attracting increasing attention in recent years. However, its metabolic fate in vivo is still unknown. To clarify its metabolism and the distribution of its metabolites in rats after oral administration, the HPLC-ESI-IT-TOF-MSn technique was used. A total of 165 new metabolites (13 phase I and 152 phase II metabolites) were tentatively identified, and 104, 29, 38, 41, 74, 28, 24, 15, 42, 8, 10, 3, and 17 metabolites were identified in urine, feces, plasma, the colon, intestine, stomach, liver, spleen, kidney, lung, heart, brain, and thymus, respectively. Metabolic reactions included demethylation, hydrogenation, hydroxylation, glucuronidation, sulfation, methylation, glycosylation, and vitamin C conjugation. M1 (medicarpin glucuronide), M5 (vestitol-1’-O-glucuronide) were distributed to 10 organs, and M1 was the most abundant metabolite in seven organs. Moreover, we found that isomerization of medicarpin must occur in vivo. At least 93 metabolites were regarded as potential new compounds by retrieving information from the Scifinder database. This is the first detailed report on the metabolism of ptercarpans in animals, which will help to deepen the understanding of the metabolism characteristics of medicarpin in vivo and provide a solid basis for further studies on the metabolism of other pterocarpans in animals.

scholarly journals Exploring the In Vivo Existence Forms (23 Original Constituents and 147 Metabolites) of Astragali Radix Total Flavonoids and Their Distributions in Rats Using HPLC-DAD-ESI-IT-TOF-MSn

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5560
Author(s):  
Li-Jia Liu ◽  
Hong-Fu Li ◽  
Feng Xu ◽  
Hong-Yan Wang ◽  
Yi-Fan Zhang ◽  
...  
Keyword(s):  
Methyl Ester ◽  
Total Flavonoids ◽  
Pharmacological Effects ◽  
Bioactive Components ◽  
Rat Urine ◽  
Astragali Radix ◽  
Material Basis ◽  
New Compounds ◽  
New Metabolites

Astragali Radix total flavonoids (ARTF) is one of the main bioactive components of Astragali Radix (AR), and has many pharmacological effects. However, its metabolism and effective forms remains unclear. The HPLC-DAD-ESI-IT-TOF-MSn technique was used to screen and tentatively identify the in vivo original constituents and metabolites of ARTF and to clarify their distribution in rats after oral administration. In addition, modern chromatographic methods were used to isolate the main metabolites from rat urine and NMR spectroscopy was used to elucidate their structures. As a result, 170 compounds (23 original constituents and 147 metabolites) were tentatively identified as forms existing in vivo, 13 of which have the same pharmacological effect with ARTF. Among 170 compounds, three were newly detected original constituents in vivo and 89 were new metabolites of ARTF, from which 12 metabolites were regarded as new compounds. Nineteen original constituents and 65 metabolites were detected in 10 organs. Four metabolites were isolated and identified from rat urine, including a new compound (calycoisn-3’-O-glucuronide methyl ester), a firstly-isolated metabolite (astraisoflavan-7-O-glucoside-2’-O-glucuronide), and two known metabolites (daidzein-7-O-sulfate and calycosin-3’-O-glucuronide). The original constituents and metabolites existing in vivo may be material basis for ARTF efficacy, and these findings are helpful for further clarifying the effective forms of ARTF.

LC-ESI-MS/MS identification and characterization of ponatinib in vivo phase I and phase II metabolites

2018 ◽  
Vol 485 ◽  
pp. 144-151 ◽  
Author(s):  
Mohamed W. Attwa ◽  
Adnan A. Kadi ◽  
Hany W. Darwish ◽  
Sawsan M. Amer ◽  
Haitham AlRabiah
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Esi Ms ◽  
Phase Ii Metabolites ◽  
Identification And Characterization

scholarly journals Urinary Excretion Kinetics of 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) and Its Phase I and Phase II Metabolites in Humans following Controlled MDMA Administration

2011 ◽  
Vol 57 (12) ◽  
pp. 1748-1756 ◽  
Author(s):  
Andrea E Schwaninger ◽  
Markus R Meyer ◽  
Allan J Barnes ◽  
Erin A Kolbrich-Spargo ◽  
David A Gorelick ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Phase I ◽  
Phase Ii ◽  
Urine Analysis ◽  
Liver Microsomes ◽  
Forensic Toxicology ◽  
Urinary Metabolites ◽  
Phase Ii Metabolites

BACKGROUND 3,4-Methylendioxymethamphetamine (MDMA) is excreted in human urine as unchanged drug and phase I and II metabolites. Previous urinary excretion studies after controlled oral MDMA administration have been performed only after conjugate cleavage. Therefore, we investigated intact MDMA glucuronide and sulfate metabolite excretion. METHODS We used LC–high-resolution MS and GC-MS to reanalyze blind urine samples from 10 participants receiving 1.0 or 1.6 mg/kg MDMA orally. We determined median Cmax, tmax, first and last detection times, and total urinary recovery; calculated ratios of sulfates and glucuronides; and performed in vitro–in vivo correlations. RESULTS Phase II metabolites of 3,4-dihydroxymethamphetamine (DHMA), 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-dihydroxyamphetamine (DHA), and 4-hydroxy-3-methoxyamphetamine were identified, although only DHMA sulfates, HMMA sulfate, and HMMA glucuronide had substantial abundance. Good correlation was observed for HMMA measured after acid hydrolysis and the sum of unconjugated HMMA, HMMA glucuronide, and HMMA sulfate (R2 = 0.87). More than 90% of total DHMA and HMMA were excreted as conjugates. The analyte with the longest detection time was HMMA sulfate. Median HMMA sulfate/glucuronide and DHMA 3-sulfate/4-sulfate ratios for the first 24 h were 2.0 and 5.3, respectively, in accordance with previous in vitro calculations from human liver microsomes and cytosol experiments. CONCLUSIONS Human MDMA urinary metabolites are primarily sulfates and glucuronides, with sulfates present in higher concentrations than glucuronides. This new knowledge may lead to improvements in urine MDMA and metabolite analysis in clinical and forensic toxicology, particularly for the performance of direct urine analysis.

Pharmacokinetics of Five Alkaloids and their Metabolites in Normal and Diabetic Rats after Oral Administration of Rhizoma coptidis

Planta Medica ◽  
2021 ◽  
Author(s):  
Xinchi Feng ◽  
Kun Wang ◽  
Shijie Cao ◽  
Liqin Ding ◽  
Feng Qiu
Keyword(s):  
Oral Administration ◽  
Diabetic Rats ◽  
Pharmacokinetic Studies ◽  
Rhizoma Coptidis ◽  
Material Basis ◽  
Diabetic Model ◽  
Long Time ◽  
Treatment Of Diabetes ◽  
Phase Ii Metabolites

AbstractRhizoma coptidis has been clinically used for a long time for the treatment of various diseases in China, such as hypertension, diabetes, and inflammation. Previous studies have shown that alkaloid components of Rhizoma coptidis extract could be extensively metabolized and the metabolites were also considered to be the therapeutic material basis. However, until now, pharmacokinetic studies of the in vivo metabolites have not been revealed yet. The aim of the present study was to characterize the pharmacokinetics and excretions of five main alkaloids (berberine, jatrorrhizine, palmatine, epiberberine, and coptisine) and their seven metabolites (berberrubine, demethyleneberberine, jatrorrhizine-3-O-β-D-glucuronide, thalifendine-10-O-β-D-glucuronide, berberrubine-9-O-β-D-glucuronide, demethyleneberberine-2-O-sulfate, and demethyleneberberine-2-O-β-D-glucuronide) in rats after oral administration of Rhizoma coptidis extract. Meanwhile, comparative pharmacokinetics and excretions of these analytes in diabetic model rats were also investigated, since Rhizoma coptidis is widely used for the treatment of diabetes. Our results showed that the in vivo existing forms of alkaloid components were phase II metabolites, highlighting the glucuronidation metabolic pathway. In diabetic model rats, the utilization of Rhizoma coptidis alkaloids was significantly increased and the biotransformation of berberine into berberrubine was significantly inhibited.

Mass Spectrometric Evaluation of Mephedrone In Vivo Human Metabolism: Identification of Phase I and Phase II Metabolites, Including a Novel Succinyl Conjugate

2014 ◽  
Vol 43 (2) ◽  
pp. 248-257 ◽  
Author(s):  
Óscar J. Pozo ◽  
María Ibáñez ◽  
Juan V. Sancho ◽  
Julio Lahoz-Beneytez ◽  
Magí Farré ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Mass Spectrometric ◽  
Human Metabolism ◽  
Phase Ii Metabolites

scholarly journals Identification of the New In Vivo Metabolites of Ilaprazole in Rat Plasma after Oral Administration by LC-MS: In Silico Prediction of the H+/K+-ATPase Inhibitor

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 459
Author(s):  
Guiqiu Zhang ◽  
Kaijing Guo ◽  
Pengfei Wang ◽  
Yingbo Shan ◽  
Chen Ma
Keyword(s):  
Oral Administration ◽  
In Silico ◽  
High Resolution Mass Spectrometry ◽  
Rat Plasma ◽  
In Silico Prediction ◽  
Atpase Inhibitor ◽  
Liquid Liquid Extraction ◽  
Oxidative Metabolites ◽  
New Metabolites

Ilaprazole is a proton pump inhibitor used to treat digestive diseases. In this study, blood samples were collected after oral administration of ilaprazole and prepared by liquid–liquid extraction. The metabolites of ilaprazole were detected by liquid chromatography–high-resolution mass spectrometry (LC-HRMS) and LC-MSn. A total of twelve in vivo metabolites were detected in rat plasma and six new metabolites of ilaprazole, including one reductive metabolite with sulfide (M3), two hydroxylated metabolites with sulfoxide (M7 and M8), and three oxidative metabolites with sulfone (M9, M11, and M12), were identified. The possible metabolic pathways of ilaprazole and the fragmentation behaviors of its metabolites were elucidated. The result of the in silico prediction indicates that all the new metabolites showed the potential ability to inhibit H+/K+-ATPase activity.

scholarly journals In Vivo Profiling and Distribution of Known and Novel Phase I and Phase II Metabolites of Efavirenz in Plasma, Urine, and Cerebrospinal Fluid

2015 ◽  
Vol 44 (1) ◽  
pp. 151-161 ◽  
Author(s):  
M. Aouri ◽  
C. Barcelo ◽  
B. Ternon ◽  
M. Cavassini ◽  
A. Anagnostopoulos ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Phase I ◽  
Phase Ii ◽  
Phase Ii Metabolites

Effects of Temperature on Metabolism of Benzo[a]pyrene by Toadfish (Opsanus beta) Hepatocytes

1990 ◽  
Vol 47 (4) ◽  
pp. 831-837 ◽  
Author(s):  
Kenneth A. Gill ◽  
Patrick J. Walsh
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
In Vivo Studies ◽  
Kinetic Properties ◽  
Opsanus Beta ◽  
Effects Of Temperature ◽  
Lower Temperature ◽  
Phase Ii Metabolites

Prior in vivo studies of the effects of temperature on uptake, metabolism and excretion of benzo[a]pyrene (BaP) by the gulf toadfish (Opsanus beta) suggested that metabolism of BaP may be partially temperature insensitive under certain conditions. In the present study, hepatocytes were isolated from toadfish acclimated to 18 or 28 °C, and then cells were exposed to BaP at 18, 23, and 28 °C in vitro to more directly examine the effects of temperature on metabolism. Toadfish hepatocytes metabolized BaP to a variety of Phase I and Phase II metabolites in similar proportions to toadfish in vivo, with the exception that fewer Phase I metabolites were detected. A marked temperature dependence of metabolism of BaP to Phase II metabolites was noted between 18 and 28 °C at near saturating concentration of BaP (13 μg∙mL−1). Warm-acclimated toadfish displayed a lower temperature sensitivity than cold-acclimated toadfish (Q10, the ratio of the rate at T + 10 °C: rate at T = 1.85 and 2.65, respectively). However, at a lower, subsaturating concentration of BaP (5 μg∙mL−1), production of all metabolites showed a marked temperature independence. We speculate that this independence is the result of temperature effects on the kinetic properties of the enzymes of xenobiotic metabolism.

Use of UPLC-HRMS/MS for In Vitro and In Vivo Metabolite Identification of Three Methylphenidate-derived New Psychoactive Substances

2019 ◽  
Vol 44 (2) ◽  
pp. 156-162
Author(s):  
Sascha K Manier ◽  
Sophia Niedermeier ◽  
Jan Schäper ◽  
Markus R Meyer
Keyword(s):  
Mass Spectrometry ◽  
Phase I ◽  
Phase Ii ◽  
Male Rats ◽  
New Psychoactive Substances ◽  
Psychoactive Substances ◽  
Screening Procedures ◽  
Phase Ii Metabolites

Abstract The distribution of so-called new psychoactive substances (NPS) as substitute for common drug of abuse was steadily increasing in the last years, but knowledge about their toxicodynamic and toxicokinetic properties is lacking. However, a comprehensive knowledge of their toxicokinetics, particularly their metabolism, is crucial for developing reliable screening procedures and to verify their intake, e.g., in case of intoxications. The aim of this study was therefore to tentatively identify the metabolites of the methylphenidate-derived NPS isopropylphenidate (isopropyl 2-phenyl-2-(2-piperidyl) acetate, IPH), 4-fluoromethylphenidate (methyl 2-(4-fluorophenyl)-2-(piperidin-2-yl) acetate, 4-FMPH) and 3,4-dichloromethylphenidate (methyl 2-(3,4-dichlorophenyl)-2-(piperidin-2-yl) acetate, 3,4-CTMP) using different in vivo and in vitro techniques and ultra-high performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS/MS). Urine samples of male rats were analyzed, and the transfer to human metabolism was done by using pooled human S9 fraction (pS9), which contains the microsomal fraction of liver homogenisate as well as its cytosol. UHPLC-HRMS/MS analysis of rat urine revealed 17 metabolites for IPH (14 phase I and 3 phase II metabolites), 13 metabolites were found for 4-FMPH (12 phase I metabolites and 1 phase II metabolite) and 7 phase I metabolites and no phase II metabolites were found for 3,4-CTMP. pS9 incubations additionally indicated that all investigated substances were primarily hydrolyzed, resulting in the corresponding carboxy metabolites. Finally, these carboxy metabolites should be used as additional analytical targets besides the parent compounds for comprehensive mass spectrometry–based screening procedures.

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