阿立哌唑口服溶液辅料橙香精中醛类物质的研究与评估

ControlofAldehydesfromOrangeEssenceinAripiprazole

关键词:  阿立哌唑口服溶液  辅料橙香精  醛类物质  PDE  风险评估

Key words:  Aripiprazole oral solution  orange essence as excipient  Aldehydes  PDE  Risk assessment

摘要:

目的 建立阿立哌唑口服溶液辅料橙香精中醛类物质检测方法,并根据PDE值评估风险,确保用药安全。方法 采用GC-MS法对橙香精中醛类物质进行筛查主要醛类物质,基于筛查结果和醛类物质引入风险,建立了小分子醛类物质“甲醛、乙醛、丙醛、辛醛、壬醛、癸醛”的衍生化HPLC检测方法,建立了“香茅醛、柠檬醛和紫苏醛”的GC检测方法。结果 经过方法学验证,各醛类物质在一定浓度范围内线性良好,R2均大于0.99；平均回收率均在91.3%~104.5%之间,准确度良好；另检测限、精密度、溶液稳定性、耐用性均良好。结论 本方法简便、快速、灵敏,可有效检测阿立哌唑口服溶液辅料橙香精中醛类物质的含量,其结果均小于各醛类物质的PDE值的30%,安全性风险较小。

Abstract:

Objective To establish a method for the detection of aldehydes in orange essence in aripiprazole oral solution, and to evaluate the risk according to the PDE value to ensure the safety of drug use. Methods The main aldehydes in orange essence were screened by GC-MS. Based on the screening results and the introduction risk of aldehydes, a derivated HPLC method for the detection of small molecule aldehydes such as formaldehyde, acetaldehyde, propanaldehyde, octyl aldehyde, nonaldehyde and capric aldehyde was established, and a GC method for the detection of citronellal, citral and perillaldehyde was established. Results The results showed that all aldehydes had good linearity in a certain concentration range with R2 greater than 0.99. The average recoveries were 91.3%~104.5%, indicating a good accuracy. In addition, the detection limit, precision, solution stability and durability are good. Conclusion The method is simple, rapid and sensitive, and can effectively detect the content of aldehydes in orange essence of aripiprazole oral solution. The results are all less than 30% of the PDE value of each aldehyde, and the safety risk is small.