Merck
  • Home
  • Search Results
  • Rapid structural characterization of in vivo and in vitro metabolites of tinoridine using UHPLC-QTOF-MS/MS and in silico toxicological screening of its metabolites.

Rapid structural characterization of in vivo and in vitro metabolites of tinoridine using UHPLC-QTOF-MS/MS and in silico toxicological screening of its metabolites.

Journal of mass spectrometry : JMS (2015-10-28)
Pradipbhai D Kalariya, Prinesh N Patel, P Kavya, Mahesh Sharma, Prabha Garg, R Srinivas, M V N Kumar Talluri
ABSTRACT

Tinoridine is a nonsteroidal anti-inflammatory drug and also has potent radical scavenger and antiperoxidative activity. However, metabolism of tinoridine has not been thoroughly investigated. To identify in vivo metabolites, the drug was administered to Sprague-Dawley rats (n = 5) at a dose of 20 mg kg(-1), and blood, urine and feces were collected at different time points up to 24 h. In vitro metabolism was delved by incubating the drug with rat liver microsomes and human liver microsomes. The metabolites were enriched by optimized sample preparation involving protein precipitation using acetonitrile, followed by solid-phase extraction. Data processes were carried out using multiple mass defects filters to eliminate false-positive ions. A total of 11 metabolites have been identified in urine samples including hydroxyl, dealkylated, acetylated and glucuronide metabolites; among them, some were also observed in plasma and feces samples. Only two major metabolites were formed using liver microsomal incubations. These metabolites were also observed in vivo. All the 11 metabolites, which are hitherto unknown and novel, were characterized by using ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry in combination with accurate mass measurements. Finally, in silico toxicological screening of all metabolites was evaluated, and two metabolites were proposed to show a certain degree of lung or liver toxicity.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Formic acid, ≥95%, FCC, FG
Sigma-Aldrich
Potassium phosphate monobasic, 99.99% trace metals basis
Sigma-Aldrich
Potassium phosphate dibasic solution, 1.0 M
Sigma-Aldrich
Acetonitrile, anhydrous, 99.8%
Sigma-Aldrich
Potassium phosphate dibasic, 99.95% trace metals basis
Sigma-Aldrich
Potassium phosphate dibasic, meets USP testing specifications
Sigma-Aldrich
Potassium phosphate dibasic, reagent grade, ≥98.0%
Sigma-Aldrich
Potassium phosphate monobasic, BioUltra, for molecular biology, anhydrous, ≥99.5% (T)
Sigma-Aldrich
Potassium phosphate dibasic, anhydrous, for luminescence, for molecular biology, BioUltra, ≥99.0% (T)
Sigma-Aldrich
Potassium phosphate monobasic, for molecular biology, ≥98.0%
Sigma-Aldrich
Potassium phosphate monobasic, powder, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99.0%
Sigma-Aldrich
Potassium phosphate monobasic, ReagentPlus®
Sigma-Aldrich
Ultrapure Acetonitrile, for DNA synthesis
Sigma-Aldrich
Acetonitrile, for DNA synthesis
Supelco
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 5 mm × 8 in.
Sigma-Aldrich
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 3 mm × 8 in.
Sigma-Aldrich
Methanol-12C, 99.95 atom % 12C
Sigma-Aldrich
Acetonitrile, for DNA synthesis
Sigma-Aldrich
Acetonitrile, electronic grade, 99.999% trace metals basis
Sigma-Aldrich
Acetonitrile, for preparative HPLC, ≥99.8% (GC)
Sigma-Aldrich
Formic acid, puriss., meets analytical specifications of DAC, FCC, 98.0-100%
Sigma-Aldrich
Formic acid, reagent grade, ≥95%
Sigma-Aldrich
Ultrapure Acetonitrile
Sigma-Aldrich
Acetonitrile
Sigma-Aldrich
Formic acid, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥98%
Sigma-Aldrich
Acetonitrile, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99.5% (GC)
Sigma-Aldrich
Acetonitrile, ACS reagent, ≥99.5%
Sigma-Aldrich
Formic acid, ACS reagent, ≥88%
Sigma-Aldrich
Potassium phosphate monobasic, buffer substance, anhydrous, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., 99.5-100.5%
Sigma-Aldrich
Formic acid, ACS reagent, ≥96%