[Application of near infrared spectroscopy to predict contents of various lactones in chromatographic process of Ginkgo Folium].

This study established a method for rapid quantification of terpene lactone, bilobalide, ginkgolide C, ginkgolide A and ginkgolide B in the chromatographic process of Ginkgo Folium based on near infrared spectroscopy(NIRS). The effects of competitive adaptive reweighting sampling(CARS), random frog(RF), and synergy interval partial least squares(siPLS) on the performance of partial least squares regression(PLSR) model were compared to the reference values measured by HPLC. Among them, the correlation coefficients of prediction(Rp) of validation sets of terpene lactone, bilobalide, and ginkgolide C were all higher than 0.98, and the relative standard errors of prediction(RSEPs) were 5.87%, 6.90% and 6.63%, respectively. Aiming at ginkgolide A and ginkgolide B with relatively low content, the genetic algorithm joint extreme learning machine(GA-ELM) was used to establish the optimized quantitative analysis model. Compared with CARS-PLSR model, the CARS-GA-ELM models of ginkgolide A and ginkgolide B exhibited a reduction in RSEP from 15.65% to 8.52% and from 21.28% to 10.84%, respectively, which met the needs of quantitative ana-lysis. It has been proved that NIRS can be used for the rapid detection of various lactone components in the chromatographic process of Ginkgo Folium.

Application of near infrared spectroscopy to predict contents of various lactones in chromatographic process of Ginkgo Folium / 中国中药杂志

This study established a method for rapid quantification of terpene lactone, bilobalide, ginkgolide C, ginkgolide A and ginkgolide B in the chromatographic process of Ginkgo Folium based on near infrared spectroscopy(NIRS). The effects of competitive adaptive reweighting sampling(CARS), random frog(RF), and synergy interval partial least squares(siPLS) on the performance of partial least squares regression(PLSR) model were compared to the reference values measured by HPLC. Among them, the correlation coefficients of prediction(Rp) of validation sets of terpene lactone, bilobalide, and ginkgolide C were all higher than 0.98, and the relative standard errors of prediction(RSEPs) were 5.87%, 6.90% and 6.63%, respectively. Aiming at ginkgolide A and ginkgolide B with relatively low content, the genetic algorithm joint extreme learning machine(GA-ELM) was used to establish the optimized quantitative analysis model. Compared with CARS-PLSR model, the CARS-GA-ELM models of ginkgolide A and ginkgolide B exhibited a reduction in RSEP from 15.65% to 8.52% and from 21.28% to 10.84%, respectively, which met the needs of quantitative ana-lysis. It has been proved that NIRS can be used for the rapid detection of various lactone components in the chromatographic process of Ginkgo Folium.

A simple and effective method for the preparation of high-purity shikimic acid from chromatography wash effluent of Ginkgo biloba leaf extract by macroporous resin considering the effect of varying feed solution compositions.

OBJECTIVES: The present study investigated the feasibility of preparing high-purity shikimic acid (SA) from the chromatography wash effluent of Ginkgo biloba leaf extract by macroporous resin. METHODS: First, static/dynamic adsorption and desorption were conducted to screen out the optimal resin. Second, the key parameters of the chromatographic process were optimised with face-centred central composite design (CCD). Third, wash effluent indices were measured, different batches of wash effluent were used to prepare SA under the optimised parameters, and the effect of varying feed solution compositions on final products was investigated. KEY FINDINGS: It was found that the final purity and recovery rate of SA prepared with ADS-21 resin were not lower than 70 and 60%, respectively, when the purity of SA in the wash effluent was higher than 21.4%. The quality of the final product can be predicted based on the properties of wash effluent. CONCLUSIONS: The proposed method could not only provide a simple, green and promising approach for the large-scale purification of SA from wash effluent but also be used to develop process intermediate quality standards for other natural products.

A Two-Step Orthogonal Chromatographic Process for Purifying the Molecular Adjuvant QS-21 with High Purity and Yield.

QS-21 is a triterpene glycoside saponin found in the bark of the Chilean soap bark tree Quillaja saponaria. It is a highly potent vaccine adjuvant that is included in two approved vaccines and has shown promise in numerous other vaccine candidates in the research and clinical pipelines. One major hurdle to the widespread use of this adjuvant is the difficulty of obtaining it in high yield and purity. Previously reported purification approaches either showed suboptimal purity and/or yield, lacked efficiency, or had strict requirement on the composition of the starting material. Here, we report the development of a new two-step orthogonal chromatographic process, consisting of a polar reversed-phase (RP) chromatography step followed by a hydrophilic interaction chromatography (HILIC) step, for purifying QS-21 from a commercially available Quillaja saponaria bark extract with high yield and > 97% purity. This process makes available a simple and efficient method for obtaining highly pure QS-21 from saponin-enriched bark extract.

[Unified form of liquid chromatography plate height equation].

The effects of radial diffusion and mobile phase heating on the column efficiency during chromatographic separation were investigated. Starting from the heat transfer equation, an equation of plate height for liquid chromatography was derived using the principle of chromatographic dynamics, with consideration of the mobile phase friction and electric heat generation:H=2γDm/u+2λdpu1/3/u1/3+ω(Dm/dp)1/3+2ku/(1+k)2(1+κ0)kd+θ(κ0+κ0k+k)2dp2u/30Dmκ0(1+κ0)2(1+k)2+κi(κ0+κ0k+k)2dp5/3u2/3/3κ0ΩDm2/3(1+κ0)2(1+k)2+r02(κ0+κ0k+k)u/4Dr(1+k)exp(-Kr02α)This equation summarized the relationship between plate heights for high performance liquid chromatography (HPLC), ultra performance liquid chromatography (UPLC), capillary electrochromatography (CEC), and eliminate stagnant fluid layer chromatography (ESFLC) and various factors. The last term in the equation represented the contribution of radial diffusion and column heating to the plate height. When the linear velocity of the mobile phase was low and the column diameter was fine, the contribution of the frictional heat generation of the mobile phase to the plate height approached zero, and the plate height equation reduced to the Horvath and Lin equation. When the linear velocity of the mobile phase was too high, friction heat was generated in the column system. The temperature difference between the axis and the edge of the column increased, resulting in a decrease in the column efficiency. The temperature difference between the axis and the edge of the column was proportional to the square of the velocity of the mobile phase. The authors clearly point out that the column efficiency in liquid chromatography is closely related to the inner diameter of the column. The use of a column with a small inner diameter is conducive to high analytical speed and high efficiency, a very high mobile phase line velocity would serious degrade the column efficiency.

Rapid process development of chromatographic process using direct analysis in real time mass spectrometry as a process analytical technology tool.

The concept of quality by design (QbD) is widely applied in the process development of pharmaceuticals. However, the additional cost and time have caused some resistance about QbD implementation. To show a possible solution, this work proposed a rapid process development method, which used direct analysis in real time mass spectrometry (DART-MS) as a process analytical technology (PAT) tool for studying the chromatographic process of Ginkgo biloba L., as an example. The breakthrough curves were fast determined by DART-MS at-line. A high correlation coefficient of 0.9520 was found between the concentrations of ginkgolide A determined by DART-MS and HPLC. Based on the PAT tool, the impacts of process parameters on the adsorption capacity were discovered rapidly, which showed a decreased adsorption capacity with the increase of the flow rate. This work has shown the feasibility and advantages of integrating PAT into QbD implementation for rapid process development.