Analysis of isoquinoline alkaloids from Mahonia leschenaultia and Mahonia napaulensis roots using UHPLC-Orbitrap-MSn and UHPLC-QqQLIT-MS/MS / 药物分析学报

Mahonia leschenaultia (ML) and Mahonia napaulensis (MN) are less known and unexplored medicinal plants of the family Berberidaceae. They are used by the Todas of Nilgiris in their religious and medical practices but chemically less identified. Hence, we decided to do extensive phytochemical analysis to explore the potential of these plant extracts. An ultrahigh performance electrospray tandem mass spectrometry (UHPLC–ESI–MS/MS) method was successfully developed for qualitative analysis of the bioactive components in Mahonia species using Orbitrap Velos Pro mass spectrometer. Sixteen compounds were identified by comparison of their retention times and mass spectra (MS) with authentic standards and reported literature. Multi-stage mass spectra (MS2–8) for the identification of protoberberine and aporphine alkaloids showed the sequential expulsion of all the substituents attached with their basic skeleton followed by CO loss. Eight of the identified compounds (berberine, jatrorrhizine, palmatine, magnoflorine, isocorydine, glaucine, tetrahydropalmatine and tetrahydroberberine) were simultaneously determined by another UHPLC–ESI–MS/MS method under the multiple reactions monitoring (MRM) mode quantitatively using triple quadrupole linear ion trap mass spectrometer. The analytical method was validated for 8 bioactive compounds with overall recovery in the range 98.5%–103.6%(RSD≤2.2%), precise (RSD≤2.07%) and linear (r≥0.9995) over the concentration range of 0.5–1000 ng/mL and successfully applied in ML and MN roots, which suggests the suitability of the proposed approach for the routine analysis of Mahonia species and their quality control.

Structural characterization of monoterpene indole alkaloids in ethanolic extracts of Rauwolfia species by liquid chromatography with quadrupole time-of-flight mass spectrometry / 药物分析学报

Rauwolfia species (Apocynaceae) are medicinal plants well known worldwide due to its potent bioactive monoterpene indole alkaloids (MIAs) such as reserpine, ajmalicine, ajmaline, serpentine and yohimbine. Reserpine, ajmalicine and ajmaline are powerful antihypertensive, tranquilizing agents used in hypertension. Yohimbine is an aphrodisiac used in dietary supplements. As there is no report on the comparative and comprehensive phytochemical investigation of the roots of Rauwolfia species, we have developed an efficient and reliable liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for ethanolic root extract of Rauwolfia species to elucidate the fragmentation pathways for dereplication of bioactive MIAs using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (HPLC–ESI–QTOF–MS/MS) in positive ion mode. We identified and established diagnostic fragment ions and fragmentation pathways using reserpine, ajmalicine, ajmaline, serpentine and yohimbine. The MS/MS spectra of reserpine, ajmalicine, and ajmaline showed C-ring-cleavage whereas E-ring cleavage was observed in serpentine via Retro Diels Alder (RDA). A total of 47 bioactive MIAs were identified and characterized on the basis of their molecular formula, exact mass measurements and MS/MS analysis. Reserpine, ajmalicine, ajmaline, serpentine and yohimbine were unambiguously identified by comparison with their authentic standards and other 42 MIAs were tentatively identified and characterized from the roots of Rauwolfia hookeri, Rauwolfia micrantha, Rauwolfia serpentina, Rauwolfia verticillata, Rauwolfia tetraphylla and Rauwolfia vomitoria. Application of LC–MS followed by principal component analysis (PCA) has been successfully used to discriminate among six Rauwolfia species.

Rapid screening and distribution of bioactive compounds in different parts of Berberis petiolaris using direct analysis in real time mass spectrometry / 药物分析学报

Berberis petiolaris Wall. ex G. Don, an unexplored medicinal plant belonging to the family Berberidaceae, is a large deciduous shrub found in Western Himalaya between 1800-3000 m. Chemical profiling of fruit, leaf, root and stem was done by direct analysis in real time mass spectrometry followed by multivariate analysis for discrimination among the plant parts. The bioactive compounds, including magnoflorine, berberine, jatrorrhizine, thalifendine/berberrubine, demethyleneberberine, reticuline, 8-oxoberberine, N-methyltetrahydroberberine, tetrahydropalmatine, tetrahydroberberine and palmatine, were identified by their exact mass measurement and the corresponding molecular formula of each compound. A comparative study of distribution pattern for all these bioactive alkaloids showed qualitative and quantitative variations in different parts of B. petiolaris. Principal component analysis clearly dis-criminated each part of B. petiolaris plant.

Characteristic differences in metabolite profile in male and female plants of dioecious Piper betle L.

Piper betle is a dioecious pan-Asiatic plant having cultural and medicinal uses. It belongs to the family Piperaceae and is a native of the tropics although it is also cultivated in subtropical areas. Flowering in P. betle occurs only in tropical regions. Due to lack of inductive floral cycles the plant remains in its vegetative state in the subtropics. Therefore, due to lack of flowering, gender distinction cannot be made the in the subtropics. Gender distinction in P. betle in vegetative state can be made using Direct Analysis in Real Time Mass Spectroscopy (DARTMS), a robust highthroughput method. DARTMS analysis of leaf samples of two male and six female plants showed characteristic differences in the spectra between male and female plants. Semi-quantitative differences in some of the identified peaks in male and female landraces showed gender-based differences in metabolites. Cluster analysis using the peaks at m/z 151, 193, 235 and 252 showed two distinct clusters of male and female landraces. It appears that male and female plants besides having flowers of different sexes also have characteristic differences in the metabolites representing two metabolic types.

Understanding the syndrome of techno-centrism through the epidemiology of vaccines as preventive tools.

Conquering disease and ill health has been an age old pursuit of man. The scientific and technological revolution of the last century ushered in major and important advances in preventive and curative medical technology which fired a new hope in the fight against communicable diseases. However, the experience over centuries shows that major decline in communicable diseases began much before the advent of modern technology due to advances in the socio-economic and environmental conditions of the people. There has been an attempt by the multilateral and unilateral agencies to supplant the expedient of technological interventions like vaccination campaigns as a substitute to socio-economic advancement in the third world countries. The dividends of this approach have been equivocal and have had an effect of distorting public health priorities in the third world. There seems to be an obsession with technology among the policy planners - a phenomenon that we call as techno-centrism; the latest example of which is the pulse polio campaign. This paper draws upon an epidemiological approach to vaccination programs as a tool to unravel this phenomenon.

Healthcare financing: Approaches and trends in India.

Despite the importance of healthcare for the well-being of society, there is little public debate in India on issues relating to it. The ‘human capital approach’ to finance healthcare largely relies on private investment in health, while the ‘human development approach’ envisages the State as the guarantor of preventive as well as curative care to achieve universalization of healthcare. The prevailing health indices of India and challenges in the field of public health require a human development approach to healthcare. On the eve of Independence, India adopted the human development approach, with the report of the Bhore Committee emphasizing the role of the State in the development and provision of healthcare. However, more recently, successive governments have moved towards the human capital approach. Instead of increasing state spending on health and expanding the public health infrastructure, the government has been relying more and more on the private sector. The public–private partnership has been touted as the new-age panacea for the ills of the Indian healthcare system. This approach has led to a stagnation of public health indices and a decrease in the access of the poor to healthcare.

Boom in clinical research industry: A dangerous trend.

Over the last decade or so India has witnessed a phenomenal growth in the clinical trial industry. The projections forecast a continuing growth of this trend. It has been predicted that by 2011 India will be in charge of 15% of global clinical trials.1 The enthusiasm for the growth of this industry in India is shared not just by the major pharmaceutical companies and CROs but also equally so by government agencies.2 The raison d’être for medical research is that it should lead to maximum possible benefit to the largest number of people. Hence, an examination of the extent to which public good is served can act as a measure for objective analysis of this exponential increase in the clinical trial industry. After all it is the health and lives of the people that are at stake. On the face of it, it would seem that all trials testing the safety and efficacy of various molecules, by their very nature work towards public welfare as they are indispensible to the development of any drug including the life-saving ones. An increasing number of clinical trials at all stages in a product’s life cycle are funded by the pharmaceutical industry.3,4 It would then seem that the industry-sponsored medical research is necessarily furthering the larger objective of human wellbeing. However, the operations of the pharmaceutical industry, the nature of the processes involved and the operative motives are a bit too complex to facilitate this larger objective so simply, just as yet. This warrants a closer look at the various aspects of industry-sponsored clinical research.