Search

The herb-pair ginseng-Fuzi (the root of Aconitum carmichaelii) is the material basis of Shenfu prescriptions and is popular in traditional Chinese medicine for the treatment of heart failure, and even shock with severe-stage of COVID-19. A narrow therapeutic window of Fuzi may cause significant regional loss of property and life in clinics. Therefore, systemic elucidation of active components is crucial to improve the safety dose window of Shenfu oral prescriptions. A high performance liquid chromatography-mass spectrometry method was developed for quantification of 10 aconitines in SD rat plasma within 9 min. The limit of detection and the limit of quantification were below 0.032 ng/ml and 0.095 ng/ml, respectively. Furthermore, a systemic comparison with their pharmacokinetic characteristics after oral administration of a safe dosage of 2 g/kg of Fuzi and ginseng-Fuzi decoction for 24 h was conducted. Eight representative diester, monoester, and non-ester aconitines and two new active components (i.e., songorine and indaconitine) were all adopted to elucidating the differences of the pharmacokinetic parameters in vivo. The compatibility of Fuzi and ginseng could significantly increase the in vivo exposure of active components. The terminal elimination half-life and the area under the concentration-time curve of mesaconitine, benzoylaconitine, benzoylmesaconitine, benzoylhypaconitine, and songorine were all increased significantly. The hypaconitine, benzoylmesaconitine, and songorine were regarded as the main active components in vivo , which gave an effective clue for the development of new Shenfu oral prescriptions. [ABSTRACT FROM AUTHOR]

Development of rapid analytical methods and establishment of toxic component limitation standards are of great importance in quality control of traditional Chinese medicine. Herein, an on-line extraction electrospray ionization mass spectrometry (oEESI-MS) coupled with a novel whole process integral quantification strategy was developed and applied to direct determination of nine key aconitine-type alkaloids in 20 Aconitum proprietary Chinese medicines (APCMs). Multi-type dosage forms (e.g. , tablets, capsules, pills, granules, and liquid preparation) of APCM could be determined directly with excellent versatility. The strategy has the characteristics of high throughput, good tolerance of matrix interference, small amount of sample (∼0.5 mg) and reagent (∼240 μL) consumption, and short analysis time for single sample (<15 min). The results were proved to be credible by high performance liquid chromatography−mass spectrometry (LC–MS) and electrospray ionization mass spectrometry, respectively. Moreover, the limitation standard for the toxic aconitines in 20 APCMs was established based on the holistic weight toxicity (HWT) evaluation and the Chinese Pharmacopoeia severally, and turned out that HWT-based toxicity evaluation results were closer to the real clinical applications. Hence, a more accurate and reliable APCM toxicity limitation was established and expected to play an important guiding role in clinics. The current study extended the power of ambient MS as a method for the direct quantification of molecules in complex samples, which is commonly required in pharmaceutical analysis, food safety control, public security, and many other disciplines. An on-line extraction electrospray ionization mass spectrometry coupled with a novel whole process integral quantification strategy was developed for direct determination of nine key alkaloids in 20 Aconitum proprietary Chinese medicines. Further, the limitation standard for the toxic aconitines was established based on the holistic weight toxicity analysis. Image 1 [ABSTRACT FROM AUTHOR]

Due to numerous obstacles such as complex matrices, real-time monitoring of complex reaction systems (e.g. , medicinal herb stewing system) has always been a challenge though great values for safe and rational use of drugs. Herein, facilitated by the potential ability on the tolerance of complex matrices of extractive electrospray ionization mass spectrometry, a device was established to realize continuous sampling and real-time quantitative analysis of herb stewing system for the first time. A complete analytical strategy, including data acquisition, data mining, and data evaluation was proposed and implemented with overcoming the usual difficulties in real-time mass spectrometry quantification. The complex Fuzi (the lateral root of Aconitum)–meat stewing systems were real-timely monitored in 150 min by qualitative and quantitative analysis of the nine key alkaloids accurately. The results showed that the strategy worked perfectly and the toxicity of the systems were evaluated and predicated accordingly. Stewing with trotters effectively accelerated the detoxification of Fuzi soup and reduced the overall toxicity to 68%, which was recommended to be used practically for treating rheumatic arthritis and enhancing immunity. The established strategy was versatile, simple, and accurate, which would have a wide application prospect in real-time analysis and evaluation of various complex reaction systems. A complete analytical strategy, including data acquisition, data mining, and data evaluation, was proposed based on the novel real-time extractive electrospray ionization mass spectrometry. The toxicity of complex Aconitum –meat stewing systems were evaluated and predicted in 150 min accurately by real-time monitoring the key aconitines. Image 1 [ABSTRACT FROM AUTHOR]

There is no effective method for unified quality evaluation for the same medicinal materials in similar prescriptions. In this study, we used Ginseng-Fuzi (Aconitum carmichaelii) proprietary Chinese medicines (GFPCMs), with different dosage forms, as examples to develop a new unified quality control strategy. Thus, using a high performance liquid chromatography-tandem mass spectrometry method, coupled with unified quality evaluation strategies to comprehensively characterize the contents of 12 aconitines and 25 ginsenosides containing eight groups of isomers in 10 GFPCMs. Quality control was carried out for the first time for aconitines and ginsenosides in Jianbuqiangshen Pill, Nanbao Capsule, Nvbao Capsule, Pingfengshengmai Capsule, Wumei Pill, and Xinbao Pill. Furthermore, 4 aconitines and 16 ginsenosides were firstly quantified in all 10 GFPCMs. Subsequently, there was a comprehensive comparison of the universality and accuracy of the quality control strategies based on absolute, normalized, and unit content. It was indicated the strategy-based unit content was more practical and effective. As for Fuzi, the total unit content of diester alkaloids should be less than 0.020%, while monoester alkaloids should be more than 0.010%. As for ginseng, the total unit content of Rb1, Rb2, Rc, Rg5, and Re should be higher than 2.0%, and the unit content of Rg5 was a good indicator for the classification of the dosage forms and processing methods. In summary, this strategy showed great potential for supervising the quality of Chinese medicine. [ABSTRACT FROM AUTHOR]

Background: The synergic action of compound prescriptions is an important feature and core advantage of traditional medicine. Ginseng-Fuzi decoction is a classic compatible phytomedicine in China, of which Ginseng can effectively reduce the toxicity of Fuzi in clinical, but the detoxification chemical mechanism is still unclear.Purpose: Develop a novel method for real-time tracking and monitoring of complex substances in the decoction system of traditional Chinese medicine to uncover the detoxification effect Ginseng on Fuzi and explore the possible chemical reaction mechanism of Ginseng-Fuzi co-decoction.Methods: A novel real-time monitoring system, online filtration electrospray ionization mass spectrometry, was developed for extremely complex substances analysis in the decoction of traditional medicine compounds to uncover the directionally detoxification effect and the mechanism of compatibility interaction.Results: Nine key alkaloids and 7 ginsenosides in Ginseng-Fuzi decoction were simultaneously in-situ monitoring in positive ion mode or negative ion mode respectively. Both types of targeted analytes had satisfactory MS signal response for real-time qualitative and quantitative analysis with high precision (RSD < 14.04%) and low LLODs (0.002 ng/ml-10 ng/ml). Through long-term tracking analysis, the exact detoxification and synergistic effect of Ginseng-Fuzi decoction were confirmed as the concentration of main toxic alkaloids decreased (e.g. the content of mesaconitine has been reduced by about 38%) and the main active monoester alkaloids increased obviously. More importantly, the possible molecular mechanism of the detoxification effect of Ginseng compatibility was revealed for the first time, which was the nucleophilic substitution reaction of diester alkaloids catalyzed by fatty acids.Conclusion: This study revealed the exact effect of co-decoction of Ginseng and Fuzi at the molecular level and the chemical reaction mechanism of fatty acid-catalyzed degradation of toxic diester-type alkaloids. The comprehensive multi-component real-time monitoring strategy for complex traditional medicine compounds developed and implemented here has important demonstration significance for revealing the scientific connotation of the compatibility of compound traditional medicine. [ABSTRACT FROM AUTHOR]

Aconitum carmichaelii Debeaux, a famous traditional medicinal herb for collapse, rheumatic fever, and painful joints, always raises global concerns about its fatal toxicity from toxic alkaloids when improperly processed. Therefore, it is urgent to clarify the internal molecular mechanism of processing detoxification on Aconitum and develop simple and reliable approaches for clinical application, which is also of great significance to the rational medicinal use of Aconitum. The study aimed at developing a complete molecular mechanism exploration strategy in complex medicinal herb decocting system, clarifying the internal molecular mechanism of processing detoxification on Aconitum, and exploring valid approaches for detoxification. Aconiti Lateralis Radix Praeparata (Fuzi) was selected as the model for exploring the complex Aconitum detoxification mechanism using an advanced online real-time platform based on extractive electrospray ionization mass spectrometry. The methods realized the sensitive capture of dynamic trace intermediates, accurate qualitative and quantitative analysis, and real-time and long-term monitoring of multi-components with satisfactory accuracy and resistance to complex matrices. Components in the complex Aconitum decocting system were real-timely characterized and fat meat was discovered and verified to directionally detoxify Aconitum while reserving the therapy effect. More importantly, the dynamic detoxification mechanism in the chemically complex Aconitum decoction was molecularly profiled. A novel reaction pathway based on nucleophilic substitution reaction mechanism was proposed. As confirmed by the theoretic calculations at DFT B3LYP/6-31G (d) levels, fatty acids (e.g. , palmitic acid) acted as a green, cheap, and high-performance catalyst and promote the decomposition of toxic diester alkaloids to non-toxic and active benzoyl-monoester alkaloids through the discovered mechanism. The study exposed a novel detoxification molecular mechanism of Aconitum and provided an effective method for the safe use of Aconitum , which could effectively guide the development of traditional processing technology and compatibility regulation of the toxic herb and had great value to the modernization and standardization development of traditional medicine. [Display omitted] • Complete molecular mechanism exploring strategies for herb decoction were developed. • Continuous monitoring on multi-components was achieved by real-time EESI-MS. • Aconitum detoxification pathway based on nucleophilic substitution was proposed. • Fat meat and fatty acid acted as favorable detoxification ingredients of Aconitum. [ABSTRACT FROM AUTHOR]

• A novel quality tracing evaluation strategy of compatible materials in 32 APCMs was developed. • The strategy includes data normalization, model development, model verification, and unknown prescription cracking. • The model was developed based on the weighted content of total 9 key alkaloids in 24 APCMs and proved reliable. • A novel prescription cracking approach was proposed to decode the unknown prescriptions. The proprietary Chinese medicine (PCM) has become a significant supplement of modern medicine. Nevertheless, the absence of quality control standard of compatible materials in PCM has led to serious adulteration, which has an extremely bad effect on safety of drug use and clinical efficacy. Here, a quality tracing evaluation strategy of compatible materials in 32 Aconitum proprietary Chinese medicines (APCMs) was established, including data normalization, model development, model verification, and unknown prescription cracking. The model was delimited based on the weighted content of total 9 key alkaloids in 24 APCMs, which were 5.65–57.10 μg/g for extract medicines and 42.62–380.61 μg/g for powder medicines. Three newly published commercial APCMs, including Wangbi Tablet, Wangbi Granule, and Fengshigutong Capsule, were used to verify its reliability and the results proved to be positive. Moreover, a novel prescription cracking approach was proposed to decode the content of each material in five unknown prescriptions including Yaoxitong Capsule, Tongrendahuoluo Pill, Xinbao Pill, Dahuoluo Capsule, and Mugua Pill. Ultimately, the single or two compatible Aconitum materials in APCMs was successfully decoded and the processed level of the materials were effectively judged. This study for the first time established a practical strategy for supervision and cracking of compatible materials in PCMs and is of great significance to improve the quality control of PCMs. [ABSTRACT FROM AUTHOR]