Quantitation of 2-hydroxyglutarate in human plasma via LC–MS/MS using a surrogate analyte approach
| Autor: | Dennis Kraus, Yonghua Ling, Hua Yang, Heidi Mangus, Feng Yin, Jennifer Keller, Guowen Liu, Rohini Narayanaswamy, Fumin Li |
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| Rok vydání: | 2020 |
| Předmět: |
Accuracy and precision
2-Hydroxyglutarate Chromatography Surrogate analyte Chemistry 010401 analytical chemistry Clinical Biochemistry General Medicine 01 natural sciences 0104 chemical sciences Analytical Chemistry Glutarates 03 medical and health sciences Medical Laboratory Technology 0302 clinical medicine Tandem Mass Spectrometry Human plasma 030220 oncology & carcinogenesis Lc ms ms Humans Biomarker (medicine) Protein precipitation In patient General Pharmacology Toxicology and Pharmaceutics Chromatography Liquid |
| Zdroj: | Bioanalysis. 12:1149-1159 |
| ISSN: | 1757-6199 1757-6180 |
| Popis: | Aim: 2-Hydroxyglutarate (2-HG) is a target engagement biomarker in patients after treatment with inhibitors of mutated isocitrate dehydrogenase (mIDH). Accurate measurement of 2-HG is critical for monitoring the inhibition effectiveness of the inhibitors. Materials & methods: Human plasma samples were spiked with stable isotope labelled internal standard, processed by protein precipitation, and analyzed using LC–MS/MS. This method was validated following regulatory guidance and has been successfully applied in a clinical study for mIDH inhibition. Results: An LC–MS/MS method with a surrogate analyte approach was developed and validated to measure 2-HG in human plasma with acceptable intra- and inter-assay accuracy and precision. Conclusion: A sensitive and robust LC–MS/MS method was developed and validated for measuring 2-HG in human plasma. |
| Databáze: | OpenAIRE |
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