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

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.