Simultaneous quantification of simvastatin and simvastatin hydroxy acid in blood serum at physiological pH by ultrahigh performance liquid chromatography–tandem mass spectrometry (UHPLC/MS/MS)
| Autor: | Charles S. Wong, Sujata Basu, Aruni Jha, Hilary J. Bews, Andrew J. Halayko, Jules C. Carlson |
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| Rok vydání: | 2014 |
| Předmět: |
Serum
Simvastatin Metabolite Clinical Biochemistry Mass spectrometry Biochemistry Uhplc ms ms Analytical Chemistry Mice chemistry.chemical_compound Blood serum Tandem Mass Spectrometry Liquid chromatography–mass spectrometry In vivo polycyclic compounds medicine Animals Chromatography High Pressure Liquid Mice Inbred BALB C Chromatography Aqueous solution Anticholesteremic Agents nutritional and metabolic diseases Cell Biology General Medicine Hydrogen-Ion Concentration chemistry Female lipids (amino acids peptides and proteins) medicine.drug |
| Zdroj: | Journal of Chromatography B. :145-150 |
| ISSN: | 1570-0232 |
| DOI: | 10.1016/j.jchromb.2013.12.030 |
| Popis: | Simvastatin attenuates airway inflammation and hyperreactivity, hallmarks of asthma, in allergen-challenged mice. As such, it is under consideration as a novel therapeutic, thus it is important to quantify the levels of simvastatin and its pharmacologically active and interconvertible metabolite, simvastatin hydroxy acid, that can be attained in the body. Methods exist to measure the concentrations of these compounds in biological media; however they do not maintain a physiological pH, and as a result do not accurately measure the ratio of these two compounds that exists in vivo. We developed a new method to measure simvastatin and simvastatin hydroxy acid more accurately in serum from mice by ultra high performance liquid chromatography-tandem mass spectrometry. We minimized the time that the compounds were in aqueous solution, and buffered samples to a physiological pH value of 7.4. Limits of quantification (LOQ) were 0.16 ng mL(-1) extract (1.3 ng mL(-1) serum) for simvastatin, and 8.3 ng mL(-1) extract (66 ng mL(-1) serum) for simvastatin hydroxy acid, respectively. No interconversion was observed, based on spike-and-recovery experiments of solutions containing both compounds. The method was applied using biological samples from mice challenged with house dust mite extract and simultaneously treated with subcutaneous simvastatin injection. Simvastatin hydroxy acid concentrations became significantly increased after a 2 week pre-treatment regime, whereas simvastatin concentrations were below the LOQ for all serum samples. |
| Databáze: | OpenAIRE |
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