Quality Control of the Fuzi Lizhong Pill Through Simultaneous Determination of 16 Major Bioactive Constituents by RRLC–MS-MS

Fuzi Lizhong pill (FLP) is used to treat gastritis, and the monarch drug of it is Aconiti Lateralis Radix Praeparata (Fuzi, aconite roots) which is a toxic herbal medicine. To better control the safety and quality of FLP, an effective method to analyze the contents of 16 toxic and bioactive components using rapid resolution liquid chromatography–tandem triple-quadrupole mass spectrometer was established. The 16 constituents included aconine, mesaconine, hypaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconine, adenosine, liquiritin, liquiritigenin, glycyrrhizic acid, isoliquiritigenin, 6-gingerol, atractylenolide III, atractylenolide I, atractylenolide II and glycyrrhetic acid. Ideal separation was performed using gradient elution in 13 min by optimized conditions. All the isomerides were isolated to baseline. The improved method with a polarity switch in contiguous time segments could analyze the five types of components, including polar and nonpolar compounds, without decreasing sensitivity. The proposed method was fully validated. The results revealed that contents of six alkaloids from Fuzi were significantly different among the samples. Using the established method and multivariate statistical method, the quality consistency of two dosage forms of FLP from different companies were analyzed. The optimized method could be used for the quality control of FLP and investigate index compound variation between two dosage forms.