ABSTRACT
UHPLC-Q-Exactive Orbitrap MS/MS was used to systematically analyze and compare the alkaloids in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata. After the samples were pretreated in the solid-phase extraction cartridges, 0.1% ammonium hydroxide(A)-acetonitrile(B) was used for gradient elution. The LC-MS method for characterization of alkaloids in the three herbal medicines was established in ESI positive ion mode to collect high resolution MS data of reference substances and samples. On the basis of the information of reference substance cracking behavior, retention time, accurate molecular mass, and related literature, a total of 155 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Prae-parata. Specifically, 130, 127, and 92 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata, respectively. Monoester alkaloids and amino-alcohol alkaloids were dominant in the three herbal medicines, and the alkaloids in Aconiti Kusnezoffii Radix and Aconiti Radix were similar. This paper can provide a reference for elucidating the pharmacological effects and clinical application differences of the three herbal medicines produced from plants of Aconitum.
Subject(s)
Tandem Mass Spectrometry , Aconitum , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal , Alkaloids , Plants, MedicinalABSTRACT
In this paper, 50 batches of representative traditional Chinese medicine tablets were selected and the disintegration time was examined with the method in Chinese Pharmacopoeia. The disintegration time and disintegration phenomenon were recorded, and the dissolution behaviors of water-soluble and ultraviolet-absorbent components during the disintegration process of tablets were characterized by self-control method. The results revealed that coating type and raw material type influenced the disintegration time of tablets. It was found that only 4% of traditional Chinese medicine tablets had obvious fragmentation during the disintegration process, while 96% of traditional Chinese medicine tablets showed gradual dissolution or dispersion. Furthermore, according to the disintegration speed, disintegration phenomenon, and whether the cumulative dissolution of measured components was > 90% at complete disintegration, a disintegration behavior classification system(DBCS) was created for the regular-release traditional Chinese medicine tablets. As a result, the disintegration behaviors of 50 batches of traditional Chinese medicine tablets were classified into four categories, i.e. ⅠA_2, ⅠB_1, ⅡB_1, and ⅡB_2. traditional Chinese medicine tablets(Class I) with disintegration time ≤ 30 min were defined to be rapid in disintegration, which can be the objective of optimization or improvement of Chinese herbal extract(semi extract) tablets. Different drug release models were used to fit the dissolution curve of traditional Chinese medicine tablets with gradual dissolution or dispersion phenomenon(i.e. Type B tablets). The results showed that the dissolution curves of water-soluble components in the disintegration process conformed to the zero order kinetics and the Ritger-Peppas model. It could be inferred that the disintegration mechanisms of type B tablets were a combination of dissolution controlled and swelling controlled mechanisms. This study contributes to understanding the disintegration behavior of traditional Chinese medicine tablets, and provides a reference for the design and improvement of disintegration performance of traditional Chinese medicine tablets.
Subject(s)
Commerce , Medicine, Chinese Traditional , Tablets , Water , Drug CompoundingABSTRACT
According to the commonly used tablet compressibility, compactability and tabletability equation, the influence of pressure range on the fitting results and parameters of different compression equations was studied, and the optimal pressure range of different equations was determined. Plastic material microcrystalline cellulose (MCC) PH102, brittle material spray dried lactose and Chinese medicine Sanqi were used as experimental objects, the compression curves of tablets were obtained by the combination of dies with different diameters. For Heckel equation, the shape of Heckel section of different materials is not uniform, and the specified linear fitting range cannot be obtained, therefore, different distances between fitting pressure starting point and starting point were set to observe the influence of pressure range on R2 of Heckel equation. The Kawakita equation, Gurnham equation, Ryshkewitch-Duckworth (R-D) equation and Power equation are fitted in three different pressure ranges of 15-200, 15-300 and 15-400 MPa, respectively. In order to find the best linear region of Heckel equation, the 3D scatter diagram of "starting point of pressure, pressure range and R2" is drawn. The best linear pressure ranges of Heckel curves of MCC, lactose and Sanqi were 20-170, 20-220 and 10-90 MPa, respectively. It is proved that the 3D scatter diagram is an effective method to find the linear range of Heckel equation. The change of pressure range has little influence on the curve fitting effect and compression parameters of Kawakita equation, Gurnham equation and Ryshkewitch-Duckworth equation. The low pressure range of 15-200 MPa can meet the fitting requirements of Kawakita equation, Gurnham equation, R-D equation and Power equation for different materials. Therefore, only by optimizing the pressure range, can the good fitting effect be ensured and the obtained compression parameters be more reliable and interpretable.
ABSTRACT
In this paper, under the guidance of quality by design (QbD) concept, the control strategy of the high shear wet granulation process of the ginkgo leaf tablet based on the design space was established to improve the process controllability and product quality consistency. The median granule size (D50) and bulk density (Da) of granules were identified as critical quality attributes (CQAs) and potential critical process parameters (pCPPs) were determined by the failure modes and effect analysis (FMEA). The Plackeet-Burmann experimental design was used to screen pCPPs and the results demonstrated that the binder amount, the wet massing time and the wet mixing impeller speed were critical process parameters (CPPs). The design space of the high shear wet granulation process was developed within pCPPs range based on the Box-Behnken design and quadratic polynomial regression models. ANOVA analysis showed that the P-values of model were less than 0.05 and the values of lack of fit test were more than 0.1, indicating that the relationship between CQAs and CPPs could be well described by the mathematical models. D₅₀ could be controlled within 170 to 500 μm, and the bulk density could be controlled within 0.30 to 0.44 g•cm⁻³ by using any CPPs combination within the scope of design space. Besides, granules produced by process parameters within the design space region could also meet the requirement of tensile strength of the ginkgo leaf tablet..
ABSTRACT
This study is aimed to propose a continual improvement strategy based on quality by design (QbD). An ultra high performance liquid chromatography (UPLC) method was developed to accomplish the method transformation from HPLC to UPLC of Panax notogineng saponins (PNS) and achieve the continual improvement of PNS based on QbD, for example. Plackett-Burman screening design and Box-Behnken optimization design were employed to further understand the relationship between the critical method parameters (CMPs) and critical method attributes (CMAs). And then the Bayesian design space was built. The separation degree of the critical peaks (ginsenoside Rg₁ and ginsenoside Re) was over 2.0 and the analysis time was less than 17 min by a method chosen from the design space with 20% of the initial concentration of the acetonitrile, 10 min of the isocratic time and 6%•min⁻¹ of the gradient slope. At last, the optimum method was validated by accuracy profile. Based on the same analytical target profile (ATP), the comparison of HPLC and UPLC including chromatograph method, CMA identification, CMP-CMA model and system suitability test (SST) indicated that the UPLC method could shorten the analysis time, improve the critical separation and satisfy the requirement of the SST. In all, HPLC method could be replaced by UPLC for the quantity analysis of PNS.
ABSTRACT
Coptis chinensis (Huanglian) is a commonly used traditional Chinese medicine (TCM) herb and alkaloids are the most important chemical constituents in it. In the present study, an isocratic reverse phase high performance liquid chromatography (RP-HPLC) method allowing the separation of six alkaloids in Huanglian was for the first time developed under the quality by design (QbD) principles. First, five chromatographic parameters were identified to construct a Plackett-Burman experimental design. The critical resolution, analysis time, and peak width were responses modeled by multivariate linear regression. The results showed that the percentage of acetonitrile, concentration of sodium dodecyl sulfate, and concentration of potassium phosphate monobasic were statistically significant parameters (P < 0.05). Then, the Box-Behnken experimental design was applied to further evaluate the interactions between the three parameters on selected responses. Full quadratic models were built and used to establish the analytical design space. Moreover, the reliability of design space was estimated by the Bayesian posterior predictive distribution. The optimal separation was predicted at 40% acetonitrile, 1.7 g·mL(-1) of sodium dodecyl sulfate and 0.03 mol·mL(-1) of potassium phosphate monobasic. Finally, the accuracy profile methodology was used to validate the established HPLC method. The results demonstrated that the QbD concept could be efficiently used to develop a robust RP-HPLC analytical method for Huanglian.
Subject(s)
Alkaloids , Bayes Theorem , Chromatography, High Pressure Liquid , Methods , Reference Standards , Chromatography, Reverse-Phase , Methods , Coptis , Chemistry , Drugs, Chinese HerbalABSTRACT
To establish a fast detection method during the purifying process of the extracts from Grardeniae using macroporous resin based on near infrared spectroscopy. First, the ethanol eluent was collected from the purification process of small size sample; and near infrared (NIR) spectrum was collected. Then the content of the geniposide was determined by HPLC method, and partial least squares (PLS) method was used to establish the quantitative model to predict the content of geniposide by NIR spectrum. This model was used to supervise the changes of geniposide concentrations in ethanol eluent during medium scale process. Experimental results showed that the NIR small scale model can accurately predict the concentrations of geniposide in the production process of medium scale. However, with the proceeding of batch processes, the prediction performance of the model was decreased, so model updating method was employed to maintain the model. After twice updates, the NIR quantitative model can accurately predict the concentrations of the geniposide during medium scale process. Therefore, through model updates, the established NIR quantitative model can be applied in different scales of macroporous resin purification processes, to improve the data utilization efficiency of small scale process and save the cost of rebuilding the quantitative model of medium scale.
ABSTRACT
It has been reported that hyperspectral data could be employed to qualitatively elucidate the spatial composition of tablets of Chinese medicinal plants. To gain more insights into this technology, a quantitative profile provided by near infrared (NIR) spectromicroscopy was further studied by determining the glycyrrhizic acid content in licorice, Glycyrrhiza uralensis. Thirty-nine samples from twenty-four different origins were analyzed using NIR spectromicroscopy. Partial least squares, interval partial least square (iPLS), and least squares support vector regression (LS-SVR) methods were used to develop linear and non-linear calibration models, with optimal calibration parameters (number of interval numbers, kernel parameter, etc.) being explored. The root mean square error of prediction (RMSEP) and the coefficient of determination (R(2)) of the iPLS model were 0.717 7% and 0.936 1 in the prediction set, respectively. The RMSEP and R(2) of LS-SVR model were 0.515 5% and 0.951 4 in the prediction set, respectively. These results demonstrated that the glycyrrhizic acid content in licorice could barely be analyzed by NIR spectromicroscopy, suggesting that good quality quantitative data are difficult to obtain from microscopic NIR spectra for complicated Chinese medicinal plant materials.