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Integrated phytochemical analysis based on UHPLC-LTQ-Orbitrap and network pharmacology approaches to explore the potential mechanism of Lycium ruthenicum Murr. for ameliorating Alzheimer's disease.
Luo, Z, Yu, G, Chen, X, Liu, Y, Zhou, Y, Wang, G, Shi, Y
Food & function. 2020;(2):1362-1372
Abstract
Based on compelling experimental and clinical evidence, the fruit of Lycium ruthenicum Murr. (LRM), a unique traditional Tibetan medicine, exerts beneficial effects on ameliorating learning and memory deficits of Alzheimer's disease (AD) and other neurodegenerative disorders. However, the potential active constituents and biological mechanism of LRM are still unknown. In this study, the major chemical constituents of LRM were first analyzed by ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap). A total of 35 constituents were confirmed or tentatively identified. Furthermore, the network-based pharmacological strategy was applied to clarify the molecular mechanism of LRM on AD based on the identified components. Totally, 143 major targets were screened and supposed to be effective players in alleviating AD. Then, the LRM chemicals-major LRM putative targets-major pathways network was constructed, implying potential biological function of LRM on AD. More importantly, 12 core genes which can be modulated by LRM were identified, and they may play a pivotal role in alleviating some major symptoms of AD. This study provided a scientific basis for further investigation and application of LRM, which demonstrated that the network pharmacology approach could be a powerful way for the mechanistic studies of folk medicines.
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Evolocumab Effects on Lipoproteins, Measured by High-Performance Liquid Chromatography.
Masuda, D, Kiyosue, A, Hirayama, A, Shimauchi, J, López, JAG, Miyawaki, K, Yamashita, S
Journal of atherosclerosis and thrombosis. 2020;(11):1183-1207
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Abstract
AIMS: Profiling of lipoproteins can predict risk of cardiovascular disease; gel permeation high-performance liquid chromatography (HPLC) improves prediction accuracy by providing detailed data for specific lipoprotein subclasses. This study applied HPLC to examine the effects of evolocumab, which effectively treats hyperlipidemia and mixed dyslipidemia, on lipoprotein subclasses, specifically the number and size of lipoprotein particles. METHODS This post-hoc analysis used patient blood samples from YUKAWA-2, a phase 3 trial evaluating the efficacy of evolocumab in Japanese adult patients with hyperlipidemia or mixed dyslipidemia and at high risk for cardiovascular disease. We used HPLC to assess observed values and percent change from baseline in cholesterol and triglyceride (TG) concentrations, number of particles in lipoprotein subclasses to week 12, and mean observed values and mean percent change from baseline in variables to weeks 10 and 12. HPLC was also compared with conventional methods in assessing low-density lipoprotein (LDL) cholesterol (LDL-C) values. RESULTS Data for all 404 patients were analyzed. Evolocumab significantly decreased cholesterol and TG concentrations, and total particle count, in very low-density lipoprotein (VLDL) and LDL subclasses. Particle size increased slightly in LDL, high-density lipoprotein (HDL), and VLDL, but data varied widely. At very low LDL-C, HPLC measurements were higher than those from conventional methods. CONCLUSION This research used HPLC to assess the effects of evolocumab in 20 lipid subclasses. By lowering lipid content and improving the lipid profile, evolocumab may reduce atherogenicity. This reduction is better quantified by HPLC than by conventional methods in the very low LDL-C range.
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A Fast and Reliable UHPLC-MS/MS-Based Method for Screening Selected Pharmacologically Significant Natural Plant Indole Alkaloids.
Tarkowská, D
Molecules (Basel, Switzerland). 2020;(14)
Abstract
Many substances of secondary plant metabolism have often attracted the attention of scientists and the public because they have certain beneficial effects on human health, although the reason for their biosynthesis in the plant remains unclear. This is also the case for alkaloids. More than 200 years have passed since the discovery of the first alkaloid (morphine), and several thousand substances of this character have been isolated since then. Most often, alkaloid-rich plants are part of folk medicine with centuries-old traditions. What is particularly important to monitor for these herbal products is the spectrum and concentrations of the present active substances, which decide whether the product has a beneficial or toxic effect on human health. In this work, we present a fast, reliable, and robust method for the extraction, preconcentration, and determination of four selected alkaloids with an indole skeleton, i.e., harmine, harmaline, yohimbine, and ajmalicine, by ultra-high performance liquid chromatography coupled with tandem mass spectrometry. The applicability of the method was demonstrated for tobacco and Tribulus terrestris plant tissue, the seeds of Peganum harmala, and extract from the bark of the African tree Pausinystalia johimbe.
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Cellulose cone tip as a sorbent material for multiphase electrical field-assisted extraction of cocaine from saliva and determination by LC-MS/MS.
Sousa, DVM, Pereira, FV, Nascentes, CC, Moreira, JS, Boratto, VHM, Orlando, RM
Talanta. 2020;:120353
Abstract
A porous and hydrophilic sorbent material was used in an extraction system, assisted by electric fields, for the extraction of cocaine in saliva and subsequent determination by ultra-high-performance liquid chromatography associated with sequential triple quadrupole mass spectrometry (UHPLC-MS/MS). The cellulose-based material was characterized by scanning electron microscopy, infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction. The time and voltage variables applied in the extraction process were investigated through a Doehlert experimental design, and with the best conditions found (35min and 300 V) some validation parameters were evaluated. The established working range was 1-100 μg L-1 (R2 > 0.99), and the detection and quantification limits determined were 0.3 and 0.8 μg L-1, respectively. Recoveries from 80 to 115% and coefficient of variation ≤15 and 16% for intra-day and inter-day assays, respectively, were obtained for sample concentrations of LOQ, 5, 25, and 75 μg L-1, indicating satisfactory accuracy and precision for the proposed method. In addition, the method presented no matrix effect, and the extraction efficiency was between 56 and 70%. The results showed that the material used has adequate physicochemical characteristics and can be applied as a sorbent and electrolyte support in multiphase extractions using electric fields.
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HPTLC based approach for bioassay-guided evaluation of antidiabetic and neuroprotective effects of eight essential oils of the Lamiaceae family plants.
Romero Rocamora, C, Ramasamy, K, Meng Lim, S, Majeed, ABA, Agatonovic-Kustrin, S
Journal of pharmaceutical and biomedical analysis. 2020;:112909
Abstract
A high-performance thin-layer chromatography (HPTLC) method combined with effect-directed-analysis (EDA) was developed to screen the antioxidant, neuroprotective and antidiabetic effects in essential oils derived from lavender flower, lemon myrtle, oregano, peppermint, sage, and rosemary leaves (Lamiaceae family). HPTLC hyphenated with microchemical (DPPH•, p-anisaldehyde, and ferric chloride) derivatizations, was used to evaluate antioxidant activity, presence of phytosterols and terpenoids, and polyphenolic content, while the combination with biochemical (α-amylase and acetylcholine esterase (AChE) enzymatic) derivatizations was used to asses α-amylase and AChE inhibitory activities. The superior antioxidant activity of oregano leaf extract is attributed to the presence of high levels of aromatic compounds, like polyphenolic acids. The strongest α-amylase inhibition was observed in lemon myrtle and rosemary plus extracts due to the presence of monoterpenes. Rosemary and sage extracts exhibit the highest AChE inhibition activity, with 1 μL essential oils being more potent than the recommended daily dose of donepezil. This superior neuroprotection was attributed to the presences of di- and triterpenes that displayed strong AChE inhibition and antioxidant potential in DPPH• free radical assay. Antioxidant activity was related to phenolic content (R = 0.49), while α-amylase inhibitory activity was positively related to antioxidant activity (R = 0.20) and terpenoid/sterol content (R = 0.31). AChE inhibitory activity was correlated (R = 0.80) to the combined effect of phenolics and terpenoids. Thus, the superior AChE inhibitory and neuroprotection potential of rosemary and sage essential oils could be attributed to joint effects of main phenolic and terpene constituents. The hyphenated HPTLC method provided rapid bioanalytical profiling of highly complex essential oil samples.
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Ultra-Performance Liquid Chromatography-Ion Mobility Separation-Quadruple Time-of-Flight MS (UHPLC-IMS-QTOF MS) Metabolomics for Short-Term Biomarker Discovery of Orange Intake: A Randomized, Controlled Crossover Study.
Lacalle-Bergeron, L, Portolés, T, López, FJ, Sancho, JV, Ortega-Azorín, C, Asensio, EM, Coltell, O, Corella, D
Nutrients. 2020;(7)
Abstract
A major problem with dietary assessments is their subjective nature. Untargeted metabolomics and new technologies can shed light on this issue and provide a more complete picture of dietary intake by measuring the profile of metabolites in biological samples. Oranges are one of the most consumed fruits in the world, and therefore one of the most studied for their properties. The aim of this work was the application of untargeted metabolomics approach with the novel combination of ion mobility separation coupled to high resolution mass spectrometry (IMS-HRMS) and study the advantages that this technique can bring to the area of dietary biomarker discovery, with the specific case of biomarkers associated with orange consumption (Citrus reticulata) in plasma samples taken during an acute intervention study (consisting of a randomized, controlled crossover trial in healthy individuals). A total of six markers of acute orange consumption, including betonicines and conjugated flavonoids, were identified with the experimental data and previous literature, demonstrating the advantages of ion mobility in the identification of dietary biomarkers and the benefits that an additional structural descriptor, as the collision cross section value (CCS), can provide in this area.
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Comparative pharmacokinetic study on three formulations of Astragali Radix by an LC-MS/MS method for determination of formononetin in human plasma.
Rao, T, Gong, YF, Peng, JB, Wang, YC, He, K, Zhou, HH, Tan, ZR, Lv, LZ
Biomedical chromatography : BMC. 2019;(9):e4563
Abstract
Astragali Radix (AR) is a widely used traditional Chinese medicine for healing the cardiovascular, liver and immune systems. Recently, superfine pulverizing technology has been applied to developing novel formulations to improve bioavailability of the active constituents in herbs, such as ultrafine granular powder of AR. In this study, a universal and sensitive quantitative method based on LC-MS/MS was employed for determining formononetin, the main flavonoid in AR, in human plasma for comparative pharmacokinetics of three oral formulations of AR. Formononetin and IS (quercetin) were extracted by ethyl acetate from human plasma and were separated on a C18 column with a mobile phase consisting of acetonitrile and 0.1% formic acid. Positive-ion electrospray-ionization mode was applied in mass spectrometric detection. The quantitative method was validated with regards to selectivity, linearity, accuracy and precision, matrix effect, extraction recovery and stability, and was applied to comparing the pharmacokinetics of ultrafine granular powder (UGP), ultrafine powder (UP) and traditional decoction pieces (TDP) of AR after oral administration. The peak concentration and areas under the concentration-time curve of formononetin in UGP and UP were significantly higher than those of TDP. UGP and UP could significantly improve the bioavailability of AR in human compared with TDP after oral administration.
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Development of a simple HPLC-MS/MS method to simultaneously determine teriflunomide and its metabolite in human plasma and urine: Application to clinical pharmacokinetic study of teriflunomide sodium and leflunomide.
Yao, X, Liu, Y, Song, L, Jiang, J, Xiao, F, Liu, D, Hu, P
Biomedical chromatography : BMC. 2019;(3):e4420
Abstract
A simple high-performance liquid chromatography coupled with tandem mass spectrometry method was developed and fully validated to simultaneously determine teriflunomide (TER) and its metabolite 4-trifluoro-methylaniline oxanilic acid (4-TMOA) in human plasma and urine. Merely 50 μL plasma and 20 μL urine were employed in sample preparation using protein precipitation and direct dilution method, respectively. An Agilent Zorbax eclipse plus C18 column was selected to achieve rapid separation for TER and 4-TMOA within 3 min. Electrospray ionization under multiple reaction monitoring was used to monitor the ion transitions for TER (m/z 269.0 → 159.9), 4-TMOA (m/z 231.9 → 160.0), internal standard teriflunomide-d4 (m/z 273.0 → 164.0) and 2-amino-4-trifluoromethyl benzoic acid (m/z 203.8 → 120.1), operating in the negative ion mode. This method proved to have better accuracy and precision over concentration range of 10-5000 ng/mL in plasma as well as 10-10,000 ng/mL in urine. After a full validation, this method was successfully applied in a pharmacokinetic study of teriflunomide sodium and leflunomide in Chinese healthy volunteers.
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Miniaturized shake-flask HPLC method for determination of distribution coefficient of drugs used in inflammatory bowel diseases.
Brusač, E, Jeličić, ML, Klarić, DA, Mornar, A
Acta pharmaceutica (Zagreb, Croatia). 2019;(4):649-660
Abstract
A new method for determination of distribution coefficient of drugs azathioprine, 6-mercaptopurine and 6-thioguanine and nutrient folic acid used in the treatment of inflammatory bowel disease based on a miniaturized shake-flask and HPLC/DAD was developed. Special attention was made to the most commonly reported problems in the measurement of distribution coefficients using a shake-flask method such as mixing technique, speed and time, the temperature of experiment, type of buffer and its pH as well as n-octanol/buffer phase ratio. The concentration of compounds in the buffer is determined by HPLC directly from shake flasks or conventional 2-mL vials. The developed method was fully validated according to ICH guidelines. Furthermore, experimental data were successfully compared with lipophilicity and human intestinal absorption calculated by the use of four different theoretical approaches. The method shows potential for high-throughput measurements of a large number of compounds.
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Simultaneous determination of saflufenacil and three metabolites in five agriculture products using liquid chromatography-Tandem mass spectrometry.
Wu, C, Liu, X, Wu, X, Dong, F, Xu, J, Zheng, Y, Zheng, Y
Journal of food biochemistry. 2019;(4):e12778
Abstract
A reliable and efficient method was firstly established for the simultaneous determination of saflufenacil and its metabolites (M800H02, M800H11 and M800H35) in cereals (soybean and corn) and fruits (apple, grape and orange), based on a triple quadrupole liquid chromatography mass spectrometer. The four target compounds were extracted with acetonitrile and purified by Florisil or Florisil with octadecylsilane from the cereals and fruits. Determination of the targets was achieved within 3.5 min by using Shim-pack GIST C18 column connected to an electrospray ionization source (ESI- mode). The method showed excellent linearity (R2 > 0.9984), and the limits of quantitation were 1 µg/kg for all compounds. Average recoveries were in the range of 74.6%-108.1%, with an intra-day relative standard deviation between 0.9% and 18.3%. The inter-day relative standard deviation was less than 13.8%. The results demonstrate that this method is convenient for monitoring the residues of saflufenacil and its metabolites in food matrices. PRACTICAL APPLICATIONS Saflufenacil controls many common annual broadleaf weed efficiently, it has been developed and launched into the market by domestic enterprises. Consequently, an analysis method for monitoring saflufenacil in food sample will be urgently needed in China over the next few years. This method provides separation with good specificity within 3.5 min, which is less than previous studies. For the five matrixes, the method presented satisfactory validation parameters in terms of good linearity, low limit of quantitations, and satisfactory accuracy and precision. Therefore, the method established in this study is a valuable tool to overcome gaps in determining saflufenacil and its metabolites in cereals and fruits, in order to accurate evaluation of risk and ensure food safety.