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

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.

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.

Metabolism of (2S)-Pterosin A: Identification of the Phase I and Phase II Metabolites in Rat Urine

2012 ◽  
Vol 40 (8) ◽  
pp. 1566-1574 ◽  
Author(s):  
Yung-Ping Lee ◽  
Feng-Lin Hsu ◽  
Jaw-Jou Kang ◽  
Chien-Kuang Chen ◽  
Shoei-Sheng Lee
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Rat Urine ◽  
Phase Ii Metabolites

Microbial production of phase I and phase II metabolites of midazolam

Xenobiotica ◽  
2011 ◽  
Vol 42 (3) ◽  
pp. 285-293 ◽  
Author(s):  
Cyrille Marvalin ◽  
Mireille Denoux ◽  
Serge Pérard ◽  
Sébastien Roy ◽  
Robert Azerad
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Microbial Production ◽  
Phase Ii Metabolites

scholarly journals Phase I/II and Phase II Studies of Targeted Gene Delivery In Vivo: Intravenous Rexin-G for Chemotherapy-resistant Sarcoma and Osteosarcoma

2009 ◽  
Vol 17 (9) ◽  
pp. 1651-1657 ◽  
Author(s):  
Sant P Chawla ◽  
Victoria S Chua ◽  
Lita Fernandez ◽  
Doris Quon ◽  
Andreh Saralou ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Phase I ◽  
Phase Ii ◽  
Targeted Gene Delivery ◽  
Phase Ii Studies

Effects of Ofloxacin Administration on the Reliability of Urine Glucose Testing

1996 ◽  
Vol 30 (5) ◽  
pp. 469-472
Author(s):  
Tsong-Mei Tsai ◽  
Brian F Shea ◽  
Paul F Souney ◽  
Fred G Volinsky ◽  
Joseph M Scavone ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Tertiary Care ◽  
Urine Samples ◽  
Care Hospital ◽  
Open Label ◽  
Urine Glucose ◽  
Glucose Testing

OBJECTIVE: TO study the effects of ofloxacin on the reliability of urine glucose testing. DESIGN: Open-label, nonrandomized. SETTING: A university-affiliated tertiary care hospital, ambulatory clinic. PARTICIPANTS: Ten healthy volunteers (8 men and 2 women) aged 22-39 years. MAIN OUTCOME MEASURES: Phase I (in vitro) involved the addition of selected amounts of ofloxacin to a set of standard 50-mL urine samples prepared to simulate glycosuria. Phase II (in vivo) involved the oral administration of ofloxacin 400 mg to 10 subjects. Urine was collected: (1) immediately predose, (2) pooled 0–4 hours postdose, and (3) pooled 4–8 hours postdose. Known glucose concentrations were then added to these samples. Clinitest and Diastix tests were performed on all samples. The accuracy of these tests in determining glucose concentrations was compared among urine samples taken before and after ofloxacin dosing. RESULTS: None of the ofloxacin concentrations in phase I (0,25,50, 100, 200,400, and 800 μg/mL) influenced these testing methods at the urine glucose concentrations of 0.0%, 0.5%, 1%, and 2%. Likewise, the accuracy of these two tests was unaffected by ofloxacin administration in phase II. CONCLUSIONS: In single-dose administration, ofloxacin does not interfere with Clinitest or Diastix for determining urine glucose concentrations. Supported by a grant from the RW Johnson Pharmaceutical Research Institute. Presented in abstract form at the American College of Clinical Pharmacy 1994 Winter Practice and Research Forum, February 6–9, 1994, San Diego. CA.

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