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LC-MS/MS assay for the therapeutic drug monitoring of perampanel in children with drug-resistant epilepsy

Dai Hao-Ran, Hu Ya-Hui, Long Jia-Yi, Xia Ying, Guo Hong-Li, Xu Jing, Ding Xuan-Sheng, Chen Jing, Lu Xiao-Peng, Chen Feng

Acta Chromatographica

2023

Vol. 35, no. 2

149--160

Perampanel (PER) is the first clinically available selective antagonist of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor approved globally for the treatment of epilepsy. Studies have recently underlined the significant association between dose-exposure-effect-adverse events of PER in patients with epilepsy, so the therapeutic drug monitoring (TDM) of PER is critical in clinical practices, especially for pediatric patients with drug-resistant epilepsy. Due to several limits in previous published analytical methods, herein, we describe the development and validation of a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method for monitoring PER in human plasma samples. Protein precipitation method by acetonitrile containing PER-d5 as internal standard was applied for the sample clean-up. Formic acid (FA, 0.2 mM) in both aqueous water and acetonitrile were used as the mobile phases and the analyte was separated by an isocratic elution. Qualification and quantification were performed under positive electrospray ionization (ESI) mode using the m/z 350.3 → 219.1 and 355.3 → 220.0 ions pairs transitions for PER and PER-d5, respectively. Potential co-medicated anti-seizure medications (ASMs) have no interference to the analysis. Calibration curves were linear in the concentration range of 1.00–2,000 ng mL⁻¹ for PER. The intra- and inter-batch precision, accuracy, recovery, dilution integrity, and stability of the method were all within the acceptable criteria and no matrix effect or carryover was found. This method was then successfully implemented on the TDM of PER in Chinese children with drug-resistant epilepsy. We firstly confirmed the apparent inter- and intra-individual PER concentration variabilities and potential drug-drug interactions between PER and several concomitant ASMs occurred in Chinese pediatric patients, which were also in line with previous studies in patients of other race.

The Tradeoff between Growth and Environment: Evidence from China and the United States

Xu Jing, Li Jianjun

Problemy Ekorozwoju

2018

Vol. 13, nr 1

15--20

This paper empirically analyzes individual attitudes on the tradeoff between environment and economy, and factors that might influence such choice for two representative countries: China and the United States. Based on the World Value Survey, the Chinese are found more inclined to support environmental protection, while people from the United States choose economic growth as priority. Considering three sets of correlates of sociodemo-graphics, environmental attitude and social context, variables such as education, political affiliation and envi-ronmental consciousness show significance in influencing personal preferences, and the effect of health, age, employment and marital status demonstrates heterogeneity across countries. Such micro-level evidence on how the public weighs the economy versus environment can provide policy guidance for the government to better respond to public opinions.

Artykuł poddaje analizie indywidualne postawy odnoszące się do kompromisu pomiędzy środowiskiem a eko-nomią, a także czynniki, które mają wpływ na kształtowanie się takich postaw, w odniesieniu do dwóch ważnych krajów: Chin i USA. Według danych World Value Survey okazuje się, ze Chińczycy są bardziej skłonni wspierać ochronę środowiska, podczas gdy Amerykanie za priorytet uznają rozwój ekonomiczny. Uwzględniając trzy zbiory korelatów odnoszące się do socjodemografii, postaw wobec środowiska i kontekstu społecznego, zmienne takie jak edukacja, orientacja polityczna i świadomość ekologiczna, okazuje się, że te czynniki odgrywają istotne znaczenie w kształtowaniu indywidualnych priorytetów, a kwestie zdrowia, wieku, zatrudnienia i stanu cywilnego wypadają podobnie w różnych krajach. Dane z takiego mikro poziomu pokazują, jak ludzie indywidualnie rozstrzygają spór pomiędzy ekonomią a środowiskiem, co stanowi polityczną wskazówkę dla rządu, dzięki której można lepiej odpowiadać na nastroje społeczne.