The extent of absorption was similar for T and R, but the rate of absorption was slightly lower for T. While such differences are not considered as clinically relevant, formal bioequivalence criteria were missed. A possible, probably indirect role of the MTHFR genotype in pharmacokinetics of capecitabine and/or 5-FU should be investigated in further studies.

Разработана экспрессная и чувствительная методика количественного определения метилдопы в плазме крови с применением ВЭЖХ-МС/МС. Динамический диапазон измерения концентраций составил 0,02-3,00 мкг/мл. Данная методика использована для проведения исследования фармакокинетики таблетированной формы метилдопы.Ключевые слова: метилдопа, ВЭЖХ-МС/МС, плазма, стабилизация, фармакокинетика. Quinta-Analytica, YaroslavlWe developed a rapid and sensitive method for quantifying plasma concentrations of methyldopa using HPLC-MS/MS. The range of concentration measurements was 0,02-3,00 g/ml. The method was applied for pharmacokinetic study of methyldopa tablet formulations.

No abstract

Разработана новая экспрессная и точная методика определения концентрации микофеноловой кислоты в плазме крови человека методом ВЭЖХ с тандемным масс-спектрометрическим детектированием (ВЭЖХ-МС/МС). Для пробоподготовки использовалась депротеинизация. Валидацию методики проводили в соответствии с Руководством по валидации биоаналитических методов EMEA и Руководством по экспертизе лекарственных средств. Данная методика использована для исследования фармакокинетики микофенолата натрия.

The approaches to bioanalytical method development for determination of substances which contain unstable functional groups in the structure are described. The oxidation and the hydrolysis are main causes of the decomposition of substances in biological fluids. Phenolic hydroxyls contain drugs were selected as examples of oxidable compounds, glucuronides of drugs were selected as examples of hydrolysable compounds. Determination of mycophenolic acid, which contains one phenolic hydroxyl and metabolized by formation of glucuronides, in plasma was performed using high performance liquid chromatography with mass-spectrometry and tandem mass-spectrometry detection. Methyldopa, which contains two phenolic hydroxyls, in stabilized plasma was assayed by high performance liquid chromatography – tandem mass-spectrometry in the range of 0.02–3.00 μg/ml. Concentrations of desmethyl mebeverine acid, which contains in the structure one phenolic hydroxyl and metabolized by formation of phenolic glucuronide, was measured simultaneously with mebeverine acid in the range of 10–2000 ng/ml. The influence of the ion source conversion of glucuronides on the quantitative determination of the substances was studied in the initial part of methods development. The next, selection of anticoagulants based on the study of short-term stability and freeze/thaw stability of the analytes and back conversion of their glucuronides was performed. The combination of anticoagulant K3EDTA and the antioxidant solution containing a mixture of ascorbic acid, sodium sulfite and sodium hydrogen carbonate in the concentrations of 5.0 %, 0.2 % and 2.4 %, respectively, was used to prevent degradation of methyldopa.