(746d) Monitoring the Whole Blending End-Point of an-Gong-Niu-Huang Wan Using the QbD Concept

[Abstract] An-Gong-Niu-Huang Wan (AGNH), a famous Chinese Materia Medica (CMM) for brain diseases, contains herbal, animal and mineral medicines such as cinnabar, realgar, Calculus Bovis, Cornu Bubali, Margarita, Borneolum Syntheticum, Rhizoma Coptidis, Radix Scutellariae, and other components. Thus, the whole end-point determination of AGNH is very significant. Based on Quality by Design (QbD) concept, Laser induced breakdown spectroscopy (LIBS) was used to assess the cinnabar, realgar and pearl powder blending of AGNH in a pilot-scale experiment, especially the whole blending end-point determination. The blending variability of three mineral medicines including cinnabar, realgar and pearl powder, was measured by moving window relative standard deviation (MWRSD). The blending was separated four phases. The time profiles of cinnabar and realgar was in tune at the last phase of blending, though not always consistent in other phases. Meanwhile, pearl powder showed similar blending behavior. At the first phase, blending was effective and efficient. But at phase B, blending tended to stable. With further time, blending became violently at phase C. The steady state then appeared in phase D. Generally, the terminal blending stage of element arsenic, mercury and calcium was phase D. Thus, the whole proposal blending end- point of element arsenic, mercury and calcium was detemined rapidly. LIBS is a promising Process Analytical Technology (PAT). Unlike other elemental determination technology, LIBS does not need an elaborate digestion procedure, which is a promising and rapid technique to understand the blending process of CMM containing cinnabar, realgar and other mineral medicines. This study proposed a novel method for the research of large varieties of traditional Chinese Medicine.

[Key words] An-Gong-Niu-Huang Wan, whole blending end-point, Laser-induced breakdown spectroscopy, Quality by Design, Process Analytical Technology