Validated HPLC-MS/MS method for quantification of ethylmethylhydroxypyridine succinate in rat brain and its application to a pharmacokinetic study
Melnik E. V., Petukhov A. E., Kozin S. V., Pomerantseva T. Y., Ramenskaya G. V.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Vol.1096, P. 180-186
Опубликовано: 2018
Тип ресурса: Статья
DOI:10.1016/j.jchromb.2018.08.029
Аннотация:
2-ethyl-6-methyl-3-hydroxypyridine (EMHP) succinate is the original antioxidant and antihypoxic drug commonly prescribed in Russia. The objective of this study was to develop a rapid, simple and sensitive high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) method for EMHP quantitation in rat brain tissue with the use of a bead beating homogenizer. The comparison between two approaches to brain tissue preparation was performed, when spiking the blank brain tissue with EMHP reference standard and internal standard (IS) before and after homogenization step. Chromatographic separation was achieved using Zorbax Eclipse Plus C18 column (1.8 μm, 2.1 × 50 mm) and elution was performed with the mobile phase, consisting of 10 mM of ammonium formate aqueous solution with 0.1[%] formic acid as solvent A and 0.1[%] formic acid in methanol as solvent B [44[%](А):56[%](В), v/v]. Flow rate was 0.4 mL/min and the total run time for each sample analysis was 2.0 min. EMHP and amantadine,
Ключевые слова:
Bead beating; Ethylmethylhydroxypyridine succinate; Homogenization; HPLC-MS/MS
Amines; Antiviral agents; Brain; Drug products; Formic acid; High performance liquid chromatography; Homogenization method; Mass spectrometry; Organic solvents; Rats; Solutions; Tissue; Chromatographic separations; Ethylmethylhydroxypyridine succinate; HPLC-MS/MS; Intraperitoneal administration; Multiple-reaction monitoring modes; Pharmacokinetic studies; Reference standard; Tandem mass spectrometry; Tissue engineering; amantadine; ammonium formate; antioxidant; ethylmethylhydroxypyridine succinate; formic acid; methanol; unclassified drug; ethylmethylhydroxypyridine succinate; pyridine derivative; animal tissue; Article; blood brain barrier; brain; brain homogenate; brain tissue; drug stability; high performance liquid chromatography; male; maximum concentration; measurement accuracy; nonhuman; pharmacokinetic parameters; plasma concentration-time curve; priority journal; rat; tandem mass spectrometry; animal; brain chemistry; chemistry; high performance liquid chromatography; procedu
Язык текста: Английский
ISSN: 1873-376X
Melnik E. V.
Petukhov A. E. Aleksej Evgenyevich 1985-
Kozin S. V.
Pomerantseva T. Y.
Ramenskaya G. V. Galina Vladislavovna 1972-
Мелник Е. В.
Петухов А. Е. Алексей Евгеньевич 1985-
Козин С. В.
Померанцева Т. Y.
Раменская Г. В. Галина Владиславовна 1972-
Validated HPLC-MS/MS method for quantification of ethylmethylhydroxypyridine succinate in rat brain and its application to a pharmacokinetic study
Текст визуальный непосредственный
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Elsevier Science Publisher B.V.
Vol.1096 P. 180-186
2018
Статья
Bead beating Ethylmethylhydroxypyridine succinate Homogenization HPLC-MS/MS
Amines Antiviral agents Brain Drug products Formic acid High performance liquid chromatography Homogenization method Mass spectrometry Organic solvents Rats Solutions Tissue Chromatographic separations Ethylmethylhydroxypyridine succinate HPLC-MS/MS Intraperitoneal administration Multiple-reaction monitoring modes Pharmacokinetic studies Reference standard Tandem mass spectrometry Tissue engineering amantadine ammonium formate antioxidant ethylmethylhydroxypyridine succinate formic acid methanol unclassified drug ethylmethylhydroxypyridine succinate pyridine derivative animal tissue Article blood brain barrier brain brain homogenate brain tissue drug stability high performance liquid chromatography male maximum concentration measurement accuracy nonhuman pharmacokinetic parameters plasma concentration-time curve priority journal rat tandem mass spectrometry animal brain chemistry chemistry high performance liquid chromatography procedu
2-ethyl-6-methyl-3-hydroxypyridine (EMHP) succinate is the original antioxidant and antihypoxic drug commonly prescribed in Russia. The objective of this study was to develop a rapid, simple and sensitive high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) method for EMHP quantitation in rat brain tissue with the use of a bead beating homogenizer. The comparison between two approaches to brain tissue preparation was performed, when spiking the blank brain tissue with EMHP reference standard and internal standard (IS) before and after homogenization step. Chromatographic separation was achieved using Zorbax Eclipse Plus C18 column (1.8 μm, 2.1 × 50 mm) and elution was performed with the mobile phase, consisting of 10 mM of ammonium formate aqueous solution with 0.1[%] formic acid as solvent A and 0.1[%] formic acid in methanol as solvent B [44[%](А):56[%](В), v/v]. Flow rate was 0.4 mL/min and the total run time for each sample analysis was 2.0 min. EMHP and amantadine,