Development and application of an LC-MS/MS method for pharmacokinetic study of ruxolitinib in children with hemophagocytic lymphohistiocytosis
| Autor: | Zhuo Li, Ning Sun, Qing Zhang, Hong-hao Ma, Dong Wang, Yun-ze Zhao, Chang-qing Yang, Rui Zhang, Li-bo Zhao |
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| Rok vydání: | 2022 |
| Předmět: |
Spectrometry
Mass Electrospray Ionization General Chemical Engineering General Engineering Reproducibility of Results Lymphohistiocytosis Hemophagocytic Analytical Chemistry Pyrimidines Tandem Mass Spectrometry Nitriles Humans Pyrazoles Child Chromatography High Pressure Liquid Chromatography Liquid |
| Zdroj: | Analytical Methods. 14:2293-2303 |
| ISSN: | 1759-9679 1759-9660 |
| DOI: | 10.1039/d2ay00533f |
| Popis: | Ruxolitinib (RUX), a small molecule inhibitor of JAK1/JAK2, has been identified as the possible novel targeted agent for the treatment of hemophagocytic lymphohistiocytosis (HLH). However, due to the lack of randomized clinical trials (RCTs), it is extremely difficult to determine the effective therapeutic dose for RUX in HLH patients, especially in pediatric patients. At the same time, the clinical response of pediatric patients to RUX varies greatly among individuals according to several case reports. Therefore, it is imperative to investigate the pharmacokinetic and pharmacodynamic characteristics of RUX in HLH children, and this must be based on a satisfactory method to determine the concentration of RUX. Owing to several limits of published analytical methods, herein, we describe a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method for monitoring RUX in children's plasma samples. The protein precipitation method using methanol was used for sample cleanup. The analytes were separated by gradient elution in which 2.0 mM ammonium acetate in distilled water and acetonitrile were used as mobile phases. In the positive electrospray ionization (ESI+) mode, the |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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