Discovery of Quality by Design-Based Extraction Technology and the Quality Standard of Jinhua Finger Citron Essential Oil.

Jinhua finger citron is one of the traditional specialties of Jinhua with a long history of cultivation. The current study highlighted the advantages of using the quality by design approach to optimize the ultrasonic-assisted distillation extraction of Jinhua finger citron essential oil. The yield of Jinhua finger citron essential oil was regarded as a potential critical quality attribute. Potential critical process parameters were screened by the definitive screening design. Finally, the design space of the essential oil extraction process was constructed. The optimal operating space included an auxiliary NaCl concentration range of 9-12.00%, a soak temperature range of 30-50 °C, a distillation time range of 3.5-4.00 h, an ultrasonic power range of 200-300 W, a solid-liquid ratio range of 1:3-1:3.5, and a soak time range of 40-80 min. On this basis, the relative density, refractive index, and pH values of different batches of Jinhua finger citron essential oil were checked. The involved batches were analyzed by gas chromatography (GC), and gas chromatographic fingerprints were established by identifying major compounds, including d-limonene, γ-terpinene, and 5,7-dimethoxycoumarin. Based on the "quality by design" strategy, the extraction process of Jinhua finger citron essential oil established in this study was robust, reliable, and flexible.