Abstract
Background
Ginkgo biloba leaf extract (EGBL) is one of the most commonly used and most studied herbal medicines around the world. Taking into account that previously reported HPLC-ELSD methods for terpene trilactones determination in EGBL are time-consuming with complicated sample preparation, it is reasonable and meaningful to developing a simple, sensitive and robust HPLC-MS method based on a novel analytical quality by design (AQbD) approach.
Methods
Firstly, analytical target profile (ATP) and systematic risk analysis were carried out to identify potential critical method attributes (CMAs) and critical method parameters (CMPs). Secondly, CMPs were identified using a standard partial regression coefficient method. Thirdly, Box-Behnken design (BBD) was employed to establish the quantitative relationship between CMAs and CMPs. Fourthly, the Monte Carlo simulation method was used to build hypercube design space. Then, the verification experiments were performed. Fifthly, the optimized method was validated and utilized. Finally, the paired t test was used to compare the developed method with HPLC-ELSD.
Results
After the screening experiments, flow rate of mobile phase, the proportion of formic acid in the mobile phase, gas flow rate and gas temperature were identified as CMPs. Models to quantitatively describe the relationship between CMAs and CMPs were built. The operational hypercube design spaces of the HPLC-MS method for terpene trilactones analysis in EGBL were successfully calculated and found to be robust, which led to the analytical control strategy. The verification experiments were successfully performed within the design space and model was found to be accurate. The method had been successfully used for quality analysis of development batches of EGBL and obtained almost identical results to data determinated using HPLC.
Conclusions
In this work, an analytical control strategy for HPLC-MS method for terpene trilactones analysis in EGBL was developed using AQbD concepts, which is promising for application to other Chinese medicines. The developed HPLC-MS method is an alternative method for quantification of terpene trilactones in commercial EGBL and will be applicable throughout the life cycle of the product.
PQLI Key Topics - Criticality, Design Space, and Control Strategy
