阿立哌唑口服溶液辅料橙香精中醛类物质的研究与评估

冯文; 周锐; 罗岚; 刘峰

doi:10.13748/j.cnki.issn1007-7693.20233509

阿立哌唑口服溶液辅料橙香精中醛类物质的研究与评估

Research and Evaluation of Aldehydes from Orange Essence in Aripiprazole Oral Solution

摘要

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，并根据每日允许暴露量(permitted daily exposure，PDE)值评估风险，确保用药安全。
方法采用GC-MS对橙香精中所含主要醛类物质进行筛查，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检测方法和“香茅醛、柠檬醛和紫苏醛”的GC检测方法，并根据ICH M7(R2)指导原则对橙香精中存在的醛类物质开展风险评估。
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>0.99；平均回收率均在91.3%~104.5%，准确度良好；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 permitted daily exposure(PDE) value to ensure the safety of drug use.
METHODS The main aldehydes in orange essence were screened by GC-MS. A derivated HPLC method for the detection of small molecule aldehydes such as formaldehyde, acetaldehyde, propanaldehyde, octyl aldehyde, nonaldehyde and capric aldehyde was established. Meanwhile, a GC method for the detection of citronellal, citral and perillaldehyde was established as well. A risk assessment of aldehydes present in orange flavors was carried out in accordance with ICH M7(R2) guidelines.
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 limit of detection, precision, solution stability and durability were 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.

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