Determination of metabolites of 3-chloro-4-benzyloxyphenylacetic acid (benzofenac) by GC/MS method

Koruna, Ivan; Ryska, Miroslav; Kuchař, Miroslav; Grimová, J; Roubal, Z.; Nĕmecek, O

doi:10.1002/bms.1200110306

Cited by 3 publications

(3 citation statements)

References 6 publications

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“…Stable isotopes such as deuterium and carbon-13 can be incorporated strategically into drug molecules to facilitate the elucidation of their metabolites’ structures using LC/MS and NMR. Numerous examples exist in the literature whereby investigators used 1:1 w/w mixtures of nonlabeled and isotope-labeled compounds to study in vitro and in vivo metabolic disposition of compounds ,− ,,,− ,− ,− . The separation of the molecular weights of the labeled and unlabeled analogues by a couple of mass units, while both retaining almost identical physicochemical properties, has made mass spectrometry the method of choice in simultaneously analyzing these compounds.…”

Section: Application Of Stable Isotope-labeled Compounds In Metabolis...mentioning

confidence: 99%

“…The combination of stable isotope-labeling techniques with mass spectrometry, which allows rapid acquisition and interpretation of data, has promoted greater use of these stable isotope-labeled compounds in a number of fields including absorption, distribution, metabolism, and excretion (ADME) studies. The use of stable isotope labeling to study various aspects of the metabolism and pharmacokinetics of drugs and other foreign compounds in animals and humans has been very well-documented ,,,,,− .…”

Section: Introductionmentioning

confidence: 99%

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Application of Stable Isotope-Labeled Compounds in Metabolism and in Metabolism-Mediated Toxicity Studies

Mutlib¹

2008

Chem. Res. Toxicol.

182

127

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Stable isotope-labeled compounds have been synthesized and utilized by scientists from various areas of biomedical research during the last several decades. Compounds labeled with stable isotopes, such as deuterium and carbon-13, have been used effectively by drug metabolism scientists and toxicologists to gain better understanding of drugs' disposition and their potential role in target organ toxicities. The combination of stable isotope-labeling techniques with mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy, which allows rapid acquisition and interpretation of data, has promoted greater use of these stable isotope-labeled compounds in absorption, distribution, metabolism, and excretion (ADME) studies. Examples of the use of stable isotope-labeled compounds in elucidating structures of metabolites and delineating complex metabolic pathways are presented in this review. The application of labeled compounds in mechanistic toxicity studies will be discussed by providing an example of how strategic placement of a deuterium atom in a drug molecule mitigated specific-specific renal toxicity. Other examples from the literature demonstrating the application of stable isotope-labeled compounds in understanding metabolism-mediated toxicities are presented. Furthermore, an example of how a stable isotope-labeled compound was utilized to better understand some of the gene changes in toxicogenomic studies is discussed. The interpretation of large sets of data produced from toxicogenomics studies can be a challenge. One approach that could be used to simplify interpretation of the data, especially from studies designed to link gene changes with the formation of reactive metabolites thought to be responsible for toxicities, is through the use of stable isotope-labeled compounds. This is a relatively unexplored territory and needs to be further investigated. The employment of analytical techniques, especially mass spectrometry and NMR, used in conjunction with stable isotope-labeled compounds to establish and understand mechanistic link between reactive metabolite formation, genomic, and proteomic changes and onset of toxicity is proposed. The use of stable isotope-labeled compounds in early human ADME studies as a way of identifying and possibly quantifying all drug-related components present in systemic circulation is suggested.

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Section: Application Of Stable Isotope-labeled Compounds In Metabolis...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Application of Stable Isotope-Labeled Compounds in Metabolism and in Metabolism-Mediated Toxicity Studies

Mutlib¹

2008

Chem. Res. Toxicol.

182

127

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“…Several publications have used diazomethane to improve the volatility of carboxylic acid containing compounds for use in liquid and gas chromatography mass spectrometry [25]. However, the synthesis and storage of diazomethane is difficult due to its chemical instability and explosive nature.…”

Section: Resultsmentioning

confidence: 99%

Quantitation of zoledronic acid in murine bone by liquid chromatography coupled with tandem mass spectrometry

Raccor

Sun

Lawrence

et al. 2013

Journal of Chromatography B

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An in vitro method for extraction and quantification of zoledronic acid (ZA) from murine bone was developed. Whole mouse bones were incubated in ZA solutions with predetermined concentrations and bound ZA was subsequently extracted from bone with phosphoric acid and derivatized using trimethylsilyl diazomethane (TMS-DAM). ZA tetra-methyl phosphonate was quantified by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). This resulted in a sensitive, accurate, and precise method that was linear over three orders of magnitude (0.0250–50.0 µg/mL ZA). For quality control (QC) samples, intra-and inter-day coefficients of variance were calculated and were less than 10%. This method was then applied to an in vivo model to quantitate ZA from the femur and mandible of three mice treated with ZA for two weeks. The mean ZA extracted from the mandible was four fold higher than that extracted from the femur (3.06 ± 0.52 vs. 0.76 ± 0.09 ng/mg respectively) indicating that ZA did not distribute equally in the skeleton and had a preference to the mandible. In conclusion, a highly sensitive method to measure ZA from mouse skeleton was developed, which can be easily adapted to multiple mammalian models including humans receiving ZA treatment.

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Recent Advances in the Use of Stable Isotopes in Drug Metabolism Research

Baillie

Rettenmeier

1986

The Journal of Clinical Pharma

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Determination of metabolites of 3-chloro-4-benzyloxyphenylacetic acid (benzofenac) by GC/MS method

Cited by 3 publications

References 6 publications

Application of Stable Isotope-Labeled Compounds in Metabolism and in Metabolism-Mediated Toxicity Studies

Application of Stable Isotope-Labeled Compounds in Metabolism and in Metabolism-Mediated Toxicity Studies

Quantitation of zoledronic acid in murine bone by liquid chromatography coupled with tandem mass spectrometry

Recent Advances in the Use of Stable Isotopes in Drug Metabolism Research

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