Simultaneous Determination Of Multiple Components Research Articles

Simultaneous determination of multiple components in rat plasma by UPLC-MS/MS for pharmacokinetic studies after oral administration of Pogostemon cablin extract

Simultaneous determination of multiple components in rat plasma by UPLC-MS/MS for pharmacokinetic studies after oral administration of Pogostemon cablin extract

Simultaneous determination of multiple components in Fuke Yangrong pill by HPLC

AbstractFuke Yangrong pill, a traditional Chinese patent medicine, with the functions of nourishing qi and blood, soothing liver and relieving depression, regulating menstruation and removing blood stasis, is composed of 16 Chinese medicinal herbs. For quality control purpose, an HPLC method was established for simultaneous quantification of paeoniflorin, hesperidin and ligustilide in Fuke Yangrong pill. With acetonitrile-0.1% formic acid as mobile phase, gradient elution was carried out using Agilent ZORBAX Eclipse Plus C18 column (250 mm × 4.6 mm, 5.0 μm) at 1.0 mL min−1. Detection wavelength was set at 230 nm for paeoniflorin, 280 nm for hesperidin and ligustilide. The temperature was 30 °C. There was a good linearity between the peak area and the concentration of each component to be measured within their linear range (r ≥ 0.9994). The average recoveries were between 98.6% and 102.6% with RSDs no more than 2.93%. This method was validated to be accurate and convenient, which is suitable for the quality control of Fuke Yangrong pill.

Multi-component content determination of Dracocephalum tanguticum by quantitative analysis of multi-components by single-marker

This study aims to establish a method for the simultaneous determination of 7 active components in Dracocephalum tanguticum and to evaluate the quality of medicinal materials from different habitats. The method was established with high performance liquid chromatography(HPLC) and the gradient elution was performed with the mobile phase of acetonitrile-methanol-0.2% phosphoric acid solution at a column temperature of 35 ℃, an injection volume of 15 μL, and a flow rate of 0.6 mL·min~(-1). The detection wavelength was set as 215 nm. With rosmarinic acid as the internal reference, the relative correction factors and the content of other 6 components were calculated. The results were compared with those obtained with the external standard method. The results showed that the samples from Huangzhong county, Qinghai province had the best quality, with the highest content of p-hydroxybenzoic acid, cosmosiin, rosmarinic acid, oleanolic acid, and ursolic acid(9.29, 12.14, 6.02, 3.11, 17.67 mg·g~(-1) respectively). The samples from Chaya county, Tibet autonomous region ranked the second, with the highest content of betulin and betulinic acid(15.53, 7.17 mg·g~(-1), respectively). The method is accurate, reliable, and repeatable and suitable for the simultaneous determination of multiple components in D. tanguticum. The content of functional components varied in the samples from different producing areas and can be used as the indicator for the quality evaluation of medicinal materials.

Simultaneous determination of multiple components in rat plasma by UHPLC-sMRM for pharmacokinetic studies after oral administration of Qingjin Yiqi Granules.

As a Traditional Chinese Medicine prescription, Qingjin Yiqi Granules (QJYQ) provides an effective treatment for patients recovering from COVID-19. However, the pharmacokinetics characteristics of the main components of QJYQ in vivo are still unknown. An efficacious ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed and validated for the simultaneous determination of 33 components in rat plasma after oral administration of QJYQ. The plasma samples were precipitated with 400µL methanol/acetonitrile (1/1, v/v) and analyzed in scheduled multiple reaction monitoring mode. The linear relationship of the 33 components was good (r > 0.9928). The lower limit of quantification for 33 components ranged from 0.4-60.5ng/mL. The average recoveries and matrix effects of the analytes ranged from 72.9% to 115.0% with RSD of 1.4%-15.0%. All inter-day and intra-day RSDs were within 15.0%. After oral administration (3.15g/kg), the validated approach was effectively applied to the pharmacokinetics of main components of QJYQ. Finally, fifteen main constituents of QJYQ with large plasma exposure were obtained, including baicalin, wogonoside, wogonin, apigenin-7-O-glucuronide, verbenalin, isoferulic acid, hesperidin, liquiritin, harpagide, protocatechuic acid, p-Coumaric acid, ferulic acid, sinapic acid, liquiritin apioside and glycyrrhizic acid. The present research lays a foundation for clarifying the therapeutic material basis of QJYQ and provides a reference for further scientific research and clinical application of QJYQ.

NMR method for simultaneous determination of 21 chemical components in Danhong Injection

Danhong Injection, a compound Chinese medicine injection prepared from Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos, is used in the clinical treatment of coronary heart disease, cerebral thrombosis, myocardial infarction, angina pectoris and other cardiovascular and cerebrovascular diseases. In this study, a quantitative method for simultaneous determination of multiple components in Danhong Injection was developed based on ~1H-qNMR technology and then methodological verification was carried out. The results showed that the established method had good methodological indexes. This method can simultaneously determine the content of 21 chemical components including 6 amino acids, 4 small molecular organic acids, 5 sugars and their derivatives, 1 nucleoside, and 5 aromatic compounds in Danhong Injection. The total content accounted for about 85% of the total solid mass, which reflected the great advantage of ~1H-qNMR method in the analysis of Chinese medicine injections. The ~1H-qNMR method for simultaneous determination of multiple components in Danhong Injection developed in this study has simple operation, short analysis time, and wide application range, which has practical significance for the quality evaluation of Danhong Injection and provides reference for the development of quality control methods for Chinese medicine injections.

Simultaneous Determination of Multiple Components in Jinshui Huanxian Granules by UPLC–Orbitrap Fusion MS

Simultaneous Determination of Multiple Components in Jinshui Huanxian Granules by UPLC–Orbitrap Fusion MS

Trends in Analytical Methods for Analysis of Tobacco Products: An Overview

Abstract. Currently, due to the strong trends in policies to reduce smoking, several concerns related to quality control and regulation of tobacco products have been raised, as a great variety of products are available to consumers in the market. Considering that development of robust and selective analytical methods for tobacco and derivative products has been an important and necessary task over the years, however laborious, due to the complexity of the matrices. This work presents an overview of advances, innovation, and trends in analytical methods, focused on the chromatographic analysis of nicotine, tobacco-specific nitrosamines (TSNAs), humectants, pesticides, polycyclic aromatic hydrocarbons (PAHs) and sugars in different tobacco products. Gas chromatography (GC) coupled with different detectors is widely used to analyze nicotine, humectants and TSNAs in tobacco leaves and derivative products, while liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been frequently used to analyze TSNAs in mainstream cigarette smoke and smokeless tobacco products. Pesticides were mainly analyzed in tobacco using GC or LC coupled with mass detector (MS), while PAHs and sugars were generally analyzed in tobacco and smoke using LC-MS and GC-MS techniques, respectively. In addition to already established methods and despite the lack of a worldwide standardization of methods, significant efforts have been made to develop analytical procedures for a wide variety of tobacco products, with a broad range of innovative chromatographic methods available. In this sense, a potential trend is the possibility of simultaneous determination of multiple components aiming to reduce the analysis time. The present study examined the main works that developed or improved analytical methods for identifying and quantifying priority compounds in different tobacco matrices and aims to contribute to future research with this objective, in addition, to promoting standardization of technical terms used in this analytical area. It is noteworthy that some of the methods mentioned here have not been validated and further studies are needed in order to obtain reproducible analytical methods for regulatory purposes.
 Keywords: chromatography analyses; tobacco leaves; cigarette; cigarette smoke; smokeless tobacco products.

Simultaneous determination of multiple components in Farfarae Flos by UHPLC-DAD and its application in quality control of decoction pieces

Farfarae Flos is a frequently used traditional herbal medicine, with outstanding antitussive, anti-asthmatic and expectorant effects. The current quality standard cannot effectively evaluate the quality of decoction pieces, or reflect the quality difference between medicinal parts and impurities. Herein, a simple, rapid, and accurate ultra high-performance liquid-chromatography diode-array (UHPLC-DAD) method was established for the simultaneous determination of 14 components in Farfarae Flos within 15 minutes. Different parts of the plant (flower bud, corolla, pedicel and stem) of 20 batches of decoction pieces were determined by the established method. Chemometrics was applied to assess the proposed method and analyze the quantitative results. Principal component analysis showed that the phenolic acids, flavonoids and terpenoids were effective quality control markers for Farfarae Flos. The quality of traditional medicinal part (flower bud) was significantly different from that of impurities (pedicel and stem). ANOVA showed that the content of phenolic acids in the pedicel and stem was significantly higher than that in the flower bud, while the content of flavonoids in the pedicel and stem was significantly lower than that in the flower bud. This study provides an efficient and low-cost methodology with adequate sensitivity for the quality control of Farfarae Flos decoction pieces.

Comparison Study on the Contents of Eight Flavonoids in three Different Processed Products of Scutellariae Radix using Ultra-high Performance Liquid Chromatography Coupled With Triple-Quadrupole Mass Spectrometry

Background: The simultaneous determination of multiple components in a sample is an important factor in the quality control of traditional Chinese medicines and can give an indication of potential clinical applications. Introduction: A rapid and sensitive method has been introduced for the simultaneous quantitative analysis of eight bioactive flavonoid constituents from Scutellariae Radix using ultra-high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. Methods: The separation was performed on a Waters Acquity UPLC C18 column (2.1 mm×100 mm, 1.7 μm), under optimized mass spectrometry conditions, with a flow rate of 0.3 mL/min. The column temperature was maintained at 35°C and the injection volume was 3 μL. Results: The method showed a good linear relationship of each component; all R2 values were above 0.9990 in the experiment. The RSDs of the precision test, repeatability test, stability test and recovery test were all not more than 2.86 %. We found that the total percentage amounts of the eight flavonoids were 22.19%, 18.63% and 10.86% in Raw Scutellariae Radix (RSR), Wine Scutellaria Radix (WSR) and Scutellaria Radix Charcoal (SRC) respectively. Conclusion: The method was successfully applied to the simultaneous determination of the eight bioactive flavonoids of Raw Scutellariae Radix, Wine Scutellaria Radix and Scutellaria Radix Charcoal.

Simultaneous determination of multiple components in rat plasma and pharmacokinetic studies at a pharmacodynamic dose of Xian-Ling-Gu-Bao capsule by UPLC-MS/MS

Xian-Ling-Gu-Bao capsule (XLGB) is an effective traditional Chinese medicine prescription (TCMP) that is used for the prevention and treatment of osteoporosis in China. A rapid, simple, efficient and stable method based on UPLC-MS/MS technology was developed for simultaneous determination of multiple components of XLGB in rat plasma. Mass spectrometric detection was performed in multiple reaction monitoring (MRM) mode with electrospray ionization (ESI). For twenty-one selected quantitative prototypes, all calibration curves showed favourable linearity (r>0.9932) in linear ranges. The lower limits of quantification (LLOQs) were 2 ng/mL for psoralen (PL), 2.5 ng/mL for asperosaponin VI (AS), 1 ng/mL for isopsoralen (IPS) and sweroside (SW), 0.5 ng/mL for magnoflorine (MA), bavachinin (BVN), tanshinone IIA (TA), timosaponin BII (TBII) and icaritin (ICT), 0.1 ng/mL for epimedin B (EB) and epimedin C (EC), 0.05 ng/mL for icariin (IC), isobavachalcone (IBC), psoralidin (PD), bavachin (BV), bavachalcone (BC), epimedin A (EA) and isobavachin (IBV), 0.02 ng/mL for neobavaisoflavone (NEO) and icariside I (ICI) and 0.01 ng/mL for icariside II (ICII). The intra-day and inter-day (low, medium, high) precision (relative standard deviation) for all analytes was less than 8.63%, and the accuracies (as relative error) were in the range of -12.45% to 8.91%. Extraction recoveries and matrix effects of analytes and IS were acceptable. All analytes were stable during the assay and storage in plasma samples. The validated method was successfully applied to the pharmacokinetics (PK) studies of the twenty-one prototypes at pharmacodynamic doses (0.3 and 1 g/kg/day). In addition, dynamic profiles of 28 metabolites (phase II conjugates: 23 glucuronide conjugates, 2 sulfate conjugates and 3 glucuronide or sulfate conjugates) were also monitored by their area/IS area-time curves. As a result, coumarins, prenylated flavonoids from Psoraleae Fructus, alkaloids and prenylated flavonol glycosides from Epimedii Herba, and iridoid glycosides, triterpenoid saponins from Dipsaci Asperoidis Radix were considered to be the key effective substances of XLGB due to their high exposure and appropriate pharmacokinetic features. This is the first report to reveal pharmacodynamic ingredients by a reversed pharmacodynamic (PD) - pharmacokinetics (PK) study.

Simultaneous determination of multiple components in formula and preparations of Xiaoyaosan

Xiaoyaosan is one of the famous formulas treating for liver, spleen and blood deficiency syndrome along Chinese history. Their five main components, paeoniflorin, ferulic acid, glycyrrhizic acid, liquiritin, and atractylenolide I are believed to partly representative of this formula. Ultra performance liquid chromatography method was newly established, UPLC BEH-C18 column (2.1 × 100 mm, 1.7 μm) with acetonitrile – 0.1% phosphate acid gradient elution system, in 0.4 mL/min and the temperature was 30 °C; Detection wavelengths were optimized separately. The five components were linear within their linear range (r ≥ 0.9991), average recovery 97.63%∼102.83%, RSD 1.88%∼4.38%. The newly established method is accurate, rapid, and convenient, with satisfied separation performance to quantify multi-components in formula and preparations of Xiaoyaosan. It will provide a reliable reference for the quality evaluation of both Xiaoyaosan formula and preparations during the process of manufacture, administration and clinical application in the future.

Simultaneous determination of multiple components in cigarettes by mechanochemical extraction and direct analysis in real time mass spectrometry in minutes

A simple, rapid and high throughput analytical approach with combination of mechanochemical extraction (MCE) and direct analysis in real time mass spectrometry (DART-MS) analysis was developed for the simultaneous determination of multiple chemical components in cigarette fillers. Different kinds of substances including nicotine, cigarette alkaloids, carbohydrates, organic acids, humectants and other additives were successfully extracted using MCE and detected by high resolution DART-MS. Six solvents of various polarities were compared during MCE process and significant differences were observed. Different brands of cigarettes as well as standard research cigarette exhibited distinctive chemical features and DART-MS fingerprints. Principle component analysis showed clear differentiation among different cigarettes extracted with the same solvent and different solvent extracts of the same type of cigarette. The putative chemical formulas were proposed based on accurate m/z values with <10 ppm mass errors. The relative contents of nicotine and other identified substances were compared and significant differences were observed among cigarettes of different locations. The whole procedure of MCE combined with DART-MS only takes minutes from raw cigarette fillers to obtaining the semi-quantitative results. The operation is simple and high throughput, providing an efficient method to analyze cigarette composition, and to establish a methodology to acquire the rapid cigarette fingerprints for quality control.

Correlation analysis between the chemical contents and bioactivity for the quality control of Alismatis Rhizoma

In order to clarify regions of production and to discriminate processing methods, quantitative and qualitative analyses for saccharides and terpenes in 35 batches of Alismatis Rhizoma were performed. Methodologies included HPLCPDA, HPLCVWD and UHPLCMSn, combined with principal component analysis (PCA) and partial least squares regression techniques (PLSR). The inhibitory effects of triterpenes and Alismatis Rhizoma extracts on lipase activity were evaluated in vitro. PLSR analysis revealed significant positive correlations (R2 = 0.5795) between the contents of triterpenes 10, 14, 15, 18 and 22 and the inhibitory effects of Alismatis Rhizoma. The present study establishes an effective method for simultaneous determination of multiple components, and identifies key bioactive triterpenes. These results can be used for systematic and novel analytical strategies for the quality control of Alismatis Rhizoma production.

Simultaneous Determination of Seven Components in Gamboge and Its Processed Products Using a Single Reference Standard

ObjectiveTo establish a quality control method for simultaneous determination of multiple components in gamboge. MethodsA single reference standard for the determination of multiple components (SSDMC) with HPLC was proposed. Seven major components of gamboge including gambogenic acid (S), β-morellic acid (C1), 2R-30-hydroxygambogic acid (C2), isogambogenic acid (C3), gambogellic acid (C4), 2R-gambogic acid (C5), and 2S-gambogic acid (C6) were simultaneously analyzed using gambogenic acid as reference standard. The credibility and feasibility of SSDMC method were validated with respect to linearity, limits of detection and quantification, precision, stability, repeatability, accuracy, ruggedness, and robustness. The relative conversion factors (RCFs) of S and C1-6 were calculated. Twelve batches of gamboge including crude and processed products were successfully analyzed by applying the SSDMC and traditional external standard (ES) methods. ResultsThe SSDMC method was credible and feasible. The RCFs of S and C1-6 were 1.000, 0.913, 0.864, 1.064, 0.777, 0.921, and 0.919, respectively. No significant difference was observed in the contents of the seven components between SSDMC and ES methods. The heat-processing technique caused a reduction in the seven components. ConclusionSSDMC is a simple, reliable, and effective method for the analysis of the complex multiple components in gamboge, and it is also a practical and economical approach.

Simultaneous Determination of Multiple Components in Guanjiekang in Rat Plasma via the UPLC-MS/MS Method and Its Application in Pharmacokinetic Study.

Guanjiekang (GJK) that is formed by five medicinal herbs including Astragali Radix, Aconiti Lateralis Radix Praeparaia, Glycyrrhizae Radix et Rhizoma, Corydalis Rhizoma and Paeoniae Radix Alba was used for the treatment of rheumatoid arthritis (RA). However, the pharmacokinetic (PK) profile of active components in GJK remains unclear. This study aims to evaluate the pharmacokinetic behavior of seven representative active constituents in GJK (i.e., benzoylhypaconine, benzoylmesaconine, paeoniflorin, tetrahydropalmatine, calycosin-7-glucoside, formononetin and isoliquiritigenin) after oral administration of GJK in rats. A rapid, sensitive and reliable ultra-performance liquid chromatography-tandem mass spectrometer (UPLC–MS/MS) method has been successfully developed for the simultaneous determination of these seven constituents in rat plasma. Chromatographic separation was achieved on a C18 column with a gradient elution program that consists of acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.35 mL/min. Detection was performed under the multiple reaction monitoring (MRM) in the positive electrospray ionization (ESI) mode. The calibration curves exhibited good linearity (R2 > 0.99) over a wide concentration range for all constituents. The accuracies ranged from 92.9% to 107.8%, and the intra-day and inter-day precisions at three different levels were below 15%. Our PK results showed that these seven compounds were quickly absorbed after the administration of the GJK product, and Tmax ranged from 30 min to 189 min. The in vivo concentrations of paeoniflorin and isoliquiritigenin were significantly higher than the reported in vitro effective doses, indicating that they could partly contribute to the therapeutic effect of GJK. Therefore, we conclude that pharmacokinetic studies of representative bioactive chemicals after administration of complex herbal products are not only necessary but also feasible. Moreover, these seven compounds that were absorbed in vivo can be used as indicator standards for quality control and for determining pharmacokinetic behavior of herbal medicines in clinical studies.

Quantification of Pharmaceutical Compounds Based on Powder X-Ray Diffraction with Chemometrics.

We propose an approach for the simultaneous determination of multiple components in pharmaceutical mixed powder based on powder X-ray diffraction (PXRD) method coupled with chemometrics. Caffeine anhydrate, acetaminophen and lactose monohydrate were mixed at various ratios. The samples were analyzed by PXRD method in the ranges of 2θ=5.00-30.0 and 35.0-45.0 degrees. Obtained diffractograms were analyzed by conventional peak intensity method, multi curve resolution (MCR)-alternating least squares (ALS) method and partial least squares (PLS) method. Constructed PLS models can most accurately predict the concentrations among different methods used. Each regression vector of PLS correlates not only to the compound of interest but also to the coexisting compounds. The combination of PXRD and PLS methods is concluded to be powerful approach for analyzing multi components in pharmaceutical formulations.

Simultaneous determination of multiple platycosides with a single reference standard in Platycodi Radix by high-performance liquid chromatography coupled with evaporative light scattering detection.

A traditional external standard method using HPLC coupled with evaporative light scattering detection has been developed for fast and accurate determination of seven platycosides in Platycodi Radix. However, inevitable difficulties in reference standards preparation process, which are quite costly and time consuming, have made its application limited. To avoid this inconvenience, a simultaneous determination of multiple components with a single reference standard strategy, which could be realized by calibrating the standard curve with internal standard and response factors, was introduced to the HPLC coupled with evaporative light scattering detection method. This is the first time that an incorporation of these two methods has been realized. Among seven ingredients, platycodin D was selected as the internal standard for its relatively easy preparation and low cost. Moreover, according to the investigation on concentration-dependent effects over response factors and robustness test, platycoside E, deapioplatycodin D, platycodin D, and polygalacin D2 were chosen to be the indicators for this novel method. The present method has not shown statistically significant differences with a traditional external standard method as verified sample analysis by the F-test (p = 95%, n = 6).

Flavone glycosides from commercially available Lophatheri Herba and their chromatographic fingerprinting and quantitation

Lophatheri Herba (Danzhuye; LH), the dried leaves of Lophatherum gracile Brongn (Poaceae), is commonly used in Chinese herbal medicine as an antipyretic, antibacterial, and diuretic. Chemical analysis has been conducted to isolate and identify seven major flavonoid glycosides, including a new flavone C-glycoside, luteolin 6-C-β-D-glucuronopyranosyl-(1→2)-β-D-glucopyranoside (1), isoorientin (2), swertiajaponin (3), luteolin 6-C-β-D-glucuronopyranosyl-(1→2)-α-L-arabinopyranoside (4), isovitexin (5), swertisin (6), luteolin 7-O-β-D-glucopyranoside (7), and luteolin 6-C-α-L-arabinopyranoside (8), from commercially available LHs in Taiwan. The structure of the new compound (1), the maximum component, was determined by extensive one- (1D-) and two-dimensional (2D-) nuclear magnetic resonance (NMR), and MS spectral analyses. The 1H and 13C-NMR of two rotameric pairs of 3 and 6 were also assigned. To establish the quality control platform of LH, we developed a simultaneous determination of multiple components in 10 commercially available LHs, collected from different areas of Taiwan, by high performance liquid chromatography (HPLC) and ultra performance liquid chromatography (UPLC), as well as quantitative measurement of the major components 1–4, and 8. All isolated major compounds showed good linear regression (R2 ≥ 0.9993) within the test ranges and high reproducibility. These methods are readily accessible for the quality control of LH.

Simultaneous determination of multiple components in explosives using ultraviolet spectrophotometry and a partial least squares method

We used UV spectrophotometry and a chemometric method to develop a novel method for the simultaneous determination of multiple components in explosives.

Genetic algorithm based multi-objective least square support vector machine for simultaneous determination of multiple components by near infrared spectroscopy

The near infrared (NIR) spectrum contains a global signature of composition, and enables to predict different proper ties of the material. In the present paper, a genetic algorithm and an adaptive modeling technique were applied to build a multiobjective least square support vector machine (MLS-SVM), which was intended to simultaneously determine the concentrations of multiple components by NIR spectroscopy. Both the benchmark corn dataset and self-made Forsythia suspense dataset were used to test the proposed approach. Results show that a genetic algorithm combined with adaptive modeling allows to efficiently search the LS-SVM hyperparameter space. For the corn data, the performance of multi-objective LS-SVM was significantly better than models built with PLS1 and PLS2 algorithms. As for the Forsythia suspense data, the performance of multi-objective LS-SVM was equivalent to PLS1 and PLS2 models. In both datasets, the over-fitting phenomena were observed on RBFNN models. The single objective LS-SVM and MLS-SVM didn't show much difference, but the one-time modeling convenience al lows the potential application of MLS-SVM to multicomponent NIR analysis.