Direct quantification of intact FIM in monkey plasma using a selective chromatography-tandem mass spectrometry method: Application in a pharmacokinetic study
| Autor: | Jianfeng Liu, Duanyun Si, Yuan Gu, Rui Wang, Shiqi Dong, Aijie Zhang, Teng Lingyan, Huirong Fan, Lu Shuixiu |
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| Rok vydání: | 2019 |
| Předmět: |
Formic acid
Clinical Biochemistry Relative standard deviation Tandem mass spectrometry 030226 pharmacology & pharmacy 01 natural sciences Biochemistry Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Glucagon-Like Peptide 1 Limit of Detection Tandem Mass Spectrometry Drug Discovery Animals Acetonitrile Molecular Biology Pharmacology chemistry.chemical_classification Chromatography Ligand binding assay 010401 analytical chemistry Reproducibility of Results General Medicine Blood Proteins 0104 chemical sciences Amino acid Chromatographic separation Macaca fascicularis chemistry Linear Models human activities Chromatography Liquid |
| Zdroj: | Biomedical chromatography : BMCREFERENCES. 34(2) |
| ISSN: | 1099-0801 |
| Popis: | FIM protein, which consists of 155 amino acids, was developed as a novel GLP-1 analog to reduce blood glucose, and pharmacodynamic results showed that it had a certain effect when used in treating Alzheimer's disease. The molecular weight of FIM is 16,304 Da. In theory, the concentration of FIM in biological samples should be determined by the ligand binding assay method or indirectly quantified using LC-MS/MS instrumentation. However, the above methods are complex and time-consuming. In this study, we successfully developed a simpler LC-MS/MS method for directly quantifying the intact FIM protein in monkey plasma for the first time. The chromatographic separation of FIM was achieved using an InertSustain Bio C18 column with a mobile phase of acetonitrile containing 0.1% formic acid (A)-water containing 0.1% formic acid (B) at a flow rate of 0.3 ml/min. Good linearity was observed in the concentration range of 5-500 ng/ml (r2 > 0.99). The intra- and inter-day precisions (expressed as relative standard deviation, RSD) of FIM were 2.30-12.8 and 7.30-13.2%, respectively. The intra- and inter-day accuracies (expressed as a relative error, RE) were -12.7-6.55 and - 10.1-0.892%, respectively. This method was successfully applied for a pharmacokinetic study of the FIM protein in four monkeys after subcutaneous administration. |
| Databáze: | OpenAIRE |
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