Development and optimization of SPE-HPLC-UV/ELSD for simultaneous determination of nine bioactive components in Shenqi Fuzheng Injection based on Quality by Design principles

Abstract

A method combining solid phase extraction, high performance liquid chromatography, and ultraviolet/evaporative light scattering detection (SPE-HPLC-UV/ELSD) was developed according to Quality by Design (QbD) principles and used to assay nine bioactive compounds within a botanical drug, Shenqi Fuzheng Injection. Risk assessment and a Plackett-Burman design were utilized to evaluate the impact of 11 factors on the resolutions and signal-to-noise of chromatographic peaks. Multiple regression and Pareto ranking analysis indicated that the sorbent mass, sample volume, flow rate, column temperature, evaporator temperature, and gas flow rate were statistically significant (p < 0.05) in this procedure. Furthermore, a Box-Behnken design combined with response surface analysis was employed to study the relationships between the quality of SPE-HPLC-UV/ELSD analysis and four significant factors, i.e., flow rate, column temperature, evaporator temperature, and gas flow rate. An analytical design space of SPE-HPLC-UV/ELSD was then constructed by calculated Monte Carlo probability. In the presented approach, the operating parameters of sample preparation, chromatographic separation, and compound detection were investigated simultaneously. Eight terms of method validation, i.e., system-suitability tests, method robustness/ruggedness, sensitivity, precision, repeatability, linearity, accuracy, and stability, were accomplished at a selected working point. These results revealed that the QbD principles were suitable in the development of analytical procedures for samples in complex matrices. Meanwhile, the analytical quality and method robustness were validated by the analytical design space. The presented strategy provides a tutorial on the development of a robust QbD-compliant quantitative method for samples in complex matrices.

Review: DNA Barcoding and Chromatography Fingerprints for the Authentication of Botanicals in Herbal Medicinal Products

“…The development of various types of mass analysers as earlier stated can make the quantitative analysis of HMP practically feasible. The HPLC-MS has been widely applied in the quantitative analysis of several HMPs such as Radix Angelicae Dahuricae [105], Yucca gloriosa L. [106], Shenqi Fuzheng injection [107], and Panax notoginseng (Sanqi) [102]. …”

Development and optimization of HPLC-MS method for simultaneous determination of four terpene trilactones in Ginkgo biloba leaf extracts based on Quality by Design principles

“…For this purpose, the method development starts with the establishment of the analytical target profile, which is the set of objectives of methods and define the intended purpose of the method. Meanwhile CMAs, an analogue of critical quality attributes (CQAs), are determined based on prior knowledge, such as the signal-to-noise ratio of target components, analysis time, the resolutions of critical peaks, and so on [25,26]. While finding CMPs is through a risk assessment and lab studies following design of experiments, just as the process of understanding critical process parameters [27].…”

“…Firstly, risk assessment and a Plackett-Burman experimental design were utilized to screen the factors [25]. The relationship between the CMAs and CMPs was determined by a Box-Behnken experimental design.…”

A novel quality by design approach for developing an HPLC method to analyze herbal extracts: A case study of sugar content analysis

“…In the meantime, the critical method attributes (CMAs) are determined primarily based on prior knowledge. Many chromatographic performance criteria can be used as CMAs, such as the resolutions of critical peaks[ 13 ], the signal-to-noise ratio (SNR) of target components[ 14 ], peak symmetry[ 15 ], peak width[ 16 ], and analysis time[ 17 ]. Secondly, parameters that have a higher probability of affecting analytical results are identified through a risk assessment approach[ 18 ], DOE method[ 19 , 20 ] or other methods.…”