RESUMO
Ainsliaea fragrans Champ, a strong heat-clearing and detoxifying traditional Chinese medicine, has been effectively used for treating chronic cervicitis, endometritis, pelvic inflammatory diseases, and other conditions caused by damp heat. It shows a good effect in the treatment of cervicitis and has broad clinical application prospects. Nevertheless, there is no comprehensive study on its in vivo and in vitro chemical analysis. UHPLC-QTOF-MS/MS combined with the non-targeted characteristic filter analysis were used to conjecture and characterize the chemical components and in vivo metabolites of rats following oral administration of Ainsliaea fragrans Champ. In this study, A total of 85 compounds were identified in Ainsliaea fragrans Champ, including 29 flavonoids, 14 sesquiterpenoids, 25 chlorogenic acids, and 17 other compounds. In the plasma of rats after administration of Ainsliaea fragrans Champ, 160 compounds were deduced (19 prototype compounds and 141 metabolites). The 141 metabolites consist of 50 flavonoids, 80 phenolic acids and 11 Chlorogenic acids. The related metabolic pathways mainly involved demethylation, reduction, sulfonation, decarboxylation, hydroxylation, methylation, and glucuronide conjunction. In summary, the chemical components and metabolites of Ainsliaea fragrans Champ were comprehensively identified by using a rapid and accurate analysis method, which laid a foundation for dissecting its bioactive substances. In addition, it provides a scientific basis for the in-depth study of the material basis of Ainsliaea fragrans Champ efficacy and theoretical support for illustrating the mechanism of medical action and its clinical application.
Assuntos
Medicamentos de Ervas Chinesas , Flavonoides , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Ratos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Administração Oral , Flavonoides/sangue , Flavonoides/química , Feminino , Ácido Clorogênico/sangue , Ácido Clorogênico/química , Ácido Clorogênico/administração & dosagem , Ácido Clorogênico/metabolismo , Asteraceae/química , Hidroxibenzoatos/sangue , Hidroxibenzoatos/análise , Hidroxibenzoatos/metabolismoRESUMO
Farfarae Flos is a traditional herb widely employed for treating coughs, bronchitis, and asthmatic disorders. In the current study, we utilized SWATH and IDA data acquisition modes in combination with multiple data processing techniques to identify Farfarae Flos metabolites in mice serum. A total of 56 compounds were characterized, including 31 phenolic acids, 13 flavonoids, 11 sesquiterpenoids and 1 alkaloid. Further quantitative analysis was conducted on 12 absorbed metabolites, utilizing a newly developed and rigorously validated analytical method. Our approach demonstrated an acceptable level of specificity, accuracy, precision, and stability. When applied to compare the serum of mice treated with FF, all 12 metabolites showed the highest concentration at 0.5 h. Overall, this study presented a novel strategy for unraveling the active compounds of FF via serum pharmacochemistry analysis, which made a foundation for exploring the pharmacodynamic material basis of FF.
Assuntos
Medicamentos de Ervas Chinesas , Animais , Cromatografia Líquida de Alta Pressão/métodos , Camundongos , Reprodutibilidade dos Testes , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Masculino , Modelos Lineares , Espectrometria de Massas/métodos , Flavonoides/sangue , Flavonoides/farmacocinética , Flavonoides/química , Limite de Detecção , Flores/química , Hidroxibenzoatos/sangue , Hidroxibenzoatos/química , Alcaloides/sangue , Alcaloides/química , Alcaloides/farmacocinéticaRESUMO
Extraction of polyphenolic metabolites from blood fractions can be challenging since compound recovery can be limited by chemical structure, polarity, and protein-binding affinity of analytes. Gallic acid and its metabolites exhibit particularly low recoveries from plasma and can lead to an underestimation of their bioavailability from foods. A modified method to extract free gallic acid and its metabolites from human plasma aided by sodium dodecyl sulfate and acidified methanol (SDS-MeOH) was applied to extract free gallic acid and its metabolites from human plasma after a single consumption of 400 g of mango (cv. Ataulfo) pulp by 10 healthy male and female subjects. The use of SDS-MeOH facilitated extraction of significantly (p < 0.05) more pyrogallol, free gallic acid, 4-O-methylgallic acid, and ethyl gallate with recovery rates exceeding 80% in standard recovery from human blood plasma when compared to conventional methods that rely on solvent extraction or solid phase extraction. The method was reproducible and precise for standards from 50 to 500 µg/L. In pharmacokinetic plasma samples five predominant metabolites of gallic acid were tentatively characterized by HPLC-MS and absorption kinetics evaluated over 8 h for catechol-O-sulfate, 4-O-methylgallic acid-3-O-sulfate, and pyrogallol-O-sulfate, methylpyrogallol-O-sulfate, and 4-O-methylgallic acid with AUC0-8h of 9520 ± 3370, 6030 ± 1310, 5990 ± 1690, 4020 ± 1040, and 2790 ± 1190 µg/L h respectively. Plasma extraction was rapid and reproducible with superior recovery rates compared to conventional methods when evaluating polar phenolic metabolites.
Assuntos
Hidroxibenzoatos/sangue , Mangifera/química , Metanol/química , Dodecilsulfato de Sódio/química , Feminino , Ácido Gálico/análogos & derivados , Ácido Gálico/sangue , Ácido Gálico/farmacocinética , Humanos , MasculinoRESUMO
BACKGROUND AND OBJECTIVES: Methyl 3,4-dihydroxybenzoate (MDHB) has the potential to prevent neurodegenerative diseases (NDDs). The present work investigated its excretion, metabolism, and cytochrome P450-based drug-drug interactions (DDIs). METHODS: After intragastric administration of MDHB, the parent drug was assayed in the urine and faeces of mice. Metabolites of MDHB in the urine, faeces, brain, plasma and liver were detected by liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). A cocktail approach was used to evaluate the inhibition of cytochrome P450 isoforms by MDHB. RESULTS: The cumulative excretion permille of MDHB in the urine and faeces were found to be 0.67 ± 0.31 and 0.49 ± 0.44, respectively. A total of 96 metabolites of MDHB were identified, and all IC50 (half-maximal inhibitory concentration) values of MDHB towards cytochrome P450 isoforms were > 100 µM. CONCLUSIONS: The results suggest that MDHB has a low parent drug cumulative excretion percentage and that MDHB has multiple metabolites and is mainly metabolized through the loss of -CH2 and -CO2, the loss of -CH2O, ester bond hydrolysis, the loss of -O and -CO2, isomerization, methylation, sulfate conjugation, the loss of -CH2O and -O and glycine conjugation, glycine conjugation, the loss of two -O groups and alanine conjugation, the loss of -CH2O and -O and glucose conjugation, glucuronidation, glucose conjugation, etc., in vivo. Finally, MDHB has a low probability of cytochrome P450-based DDIs.
Assuntos
Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Hidroxibenzoatos/metabolismo , Eliminação Renal/efeitos dos fármacos , Animais , Interações Medicamentosas , Fezes , Hidroxibenzoatos/sangue , Masculino , Camundongos , Estrutura Molecular , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/metabolismo , Isoformas de ProteínasRESUMO
Naoshuantong capsule (NSTC) is an oral traditional Chinese medicine formula used widely in the clinic for ischemic stroke. The absorbed ingredients and metabolites of NSTC have never been reported before. In this study, a method incorporating rapid resolution liquid chromatography with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to identify absorbed ingredients and metabolites after oral administration of NSTC. A total of 15 constituents were detected and identified as prototypes of NSTC. 109 metabolites related to catechin, gallic acid, paeoniflorin, chlorogenic acid, protocatechuate, typhaneoside, ß-elemene, calycosin were identified in serum, urine and brain. 19 metabolites of typhaneoside, 3 metabolites of ß-elemene, 12 metabolites of calycosin were reported for the first time. This is the first time to explore the absorption and metabolism of NSTC. The work will provide helpful information for further research of the mechanism and application of NSTC.
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Espectrometria de Massas em Tandem/métodos , Animais , Líquidos Corporais/metabolismo , Encéfalo/metabolismo , Catequina/sangue , Ácido Clorogênico/sangue , Cromatografia Líquida de Alta Pressão/métodos , Ácido Gálico/sangue , Glucosídeos/sangue , Glicosídeos/metabolismo , Hidroxibenzoatos/sangue , Isoflavonas/sangue , Masculino , Medicina Tradicional Chinesa/métodos , Metaboloma , Camundongos , Camundongos Endogâmicos C57BL , Monoterpenos/sangue , Sesquiterpenos/sangueRESUMO
Increased processing of pulses generates large volumes of hulls, which are known as an excellent source of phenolic antioxidants. However, the bioavailability and in vivo activity of these phenolics are rarely reported. This research was therefore carried out to study the absorption, metabolism, and in vivo antioxidant activities of green pea hull (GPH) phenolics using ultrahigh-pressure liquid chromatography with a linear ion trap-high-resolution Orbitrap mass spectrometry and an oxidative stress rat model. A total of 31 phenolics, including 4 phenolic acids, 24 flavonoids, and 3 other phenolics, were tentatively identified. Ten of these phenolics and 49 metabolites were found in the plasma and urine of rats, which helped to explain the favorable changes by GPH phenolics in key antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and glutathione) and indicators (total antioxidant capacity, malondialdehyde) in the plasma and different tissues of rats. This is the first comprehensive report on dry pea hull phenolics and their bioavailability, metabolic profiles, and mechanisms of in vivo antioxidant activities.
Assuntos
Antioxidantes/metabolismo , Fenóis/sangue , Fenóis/urina , Pisum sativum/metabolismo , Extratos Vegetais/sangue , Extratos Vegetais/urina , Resíduos/análise , Animais , Antioxidantes/química , Disponibilidade Biológica , Feminino , Flavonoides/sangue , Flavonoides/metabolismo , Flavonoides/urina , Hidroxibenzoatos/sangue , Hidroxibenzoatos/metabolismo , Hidroxibenzoatos/urina , Estrutura Molecular , Pisum sativum/química , Fenóis/química , Extratos Vegetais/química , Ratos , Ratos Sprague-DawleyRESUMO
SCOPE: Blueberry polyphenols are thought to confer cardiovascular health benefits, but have limited bioavailability. They undergo extensive metabolism and their phenolic acid metabolites are likely to be the mediators of bioactivity. The effect of blueberry-derived phenolic acids on one aspect of inflammation, monocyte adhesion to vascular endothelial cells, is investigated. METHODS AND RESULTS: The major blueberry-derived phenolic acids in human plasma are identified and quantified. Three test mixtures representing compounds present at 0-4 h (Early), 4-24 h (Late), or 0-24 h (Whole) are used to investigate the effect on adhesion of monocytes to tumor necrosis factor alpha (TNFα)-activated endothelial cells. The Late mixture reduces monocyte adhesion, but there is no effect of the Early or Whole mixtures. Exclusion of syringic acid from each mixture results in inhibition of monocyte adhesion. Exposure to the phenolic acid mixtures has no effect on the endothelial surface expression of adhesion molecules intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), or E-selectin, suggesting that other molecular mechanisms are responsible for the observed effect. CONCLUSION: This study shows that physiological concentrations of blueberry polyphenol metabolites can help maintain cardiovascular health by regulating monocyte adhesion to the vascular endothelium.
Assuntos
Mirtilos Azuis (Planta)/química , Hidroxibenzoatos/sangue , Hidroxibenzoatos/farmacologia , Monócitos/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Citometria de Fluxo , Ácido Gálico/análogos & derivados , Ácido Gálico/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Hidroxibenzoatos/isolamento & purificação , Monócitos/citologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Chinese medicinal herbs danshen and huangqin have attracted attention in spinal cord injury (SCI) treatment. Purpose of this study was to investigate and compare the pharmacokinetic characteristics of 4 phenolic acids and 4 flavonoids in SCI rat plasma after orally administrate danshen, huangqin and combined extract of these two herbs (CDH). Thus, a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneously quantitative determination of tanshinol, protocatechualdehyde, protocatechuic acid, salvianolic acid A, baicalein, baicalin, wogonin and wogonoside. After inducing a contusion injury by a weight-drop device, SCI rats were orally administrated a single dose (12.5 g/kg) of danshen, huangqin and CDH extracts, respectively. Then, blood samples at different time points were collected and analyzed. In CDH group, Cmax and AUC of tanshinol, protocatechualdehyde and protocatechuic acid significantly declined, while those of salvianolic acid A enhanced. These changes were beneficial for danshen to treat SCI. As for flavonoids, double peaks were observed in huangqin group, while this phenomenon disappeared in CDH group. Concomitantly, Cmax and AUC declined after administrated CDH. These alterations were due to influence of danshen active constituents on absorption and transportation process of flavonoids. Therefore, danshen and huangqin significantly influenced pharmacokinetic profile and parameters of each other, thus exert synergistic therapeutic effect in SCI treatment.
Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Salvia miltiorrhiza/química , Scutellaria baicalensis/química , Traumatismos da Medula Espinal/tratamento farmacológico , Administração Oral , Animais , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Combinação de Medicamentos , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Flavonoides/sangue , Humanos , Hidroxibenzoatos/sangue , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/etiologia , Espectrometria de Massas em TandemRESUMO
SCOPE: Black raspberries (BRB) are a rich source of bioactive phytochemicals, including anthocyanins and ellagitannins. These phytochemicals are poorly absorbed and may be transformed by gut microbiota into various metabolites that may impact the colonic mucosa or upon absorption have systemic bioactivity. The objective of this study is to define the impact of a BRB-containing diet on the colon microbiome in mice and quantify the phytochemical metabolites in the colon contents and circulation. METHODS AND RESULTS: Male mice were fed 10% w/w freeze-dried BRB powder for 6 weeks. The colonic microbiota was evaluated by 16S rRNA gene sequencing. Anthocyanin and ellagitannin metabolites, protocatechuic acid, and urolithins were analyzed by HPLC-MS/MS. The BRB diet impacted colon mucosal microbial composition with a more robust effect observed on the luminal microflora. BRB-derived protocatechuic acid and urolithins were quantified in the colon, luminal contents, plasma, liver, and prostate with protocatechuic acid present in higher concentrations compared to urolithins. CONCLUSION: This study highlights the complex interactions between dietary phytochemicals, the host microbiome, and metabolism. It is demonstrated that microbially produced phytochemical metabolites are present in the colon and systemic circulation where they may exert biological activity.
Assuntos
Colo/microbiologia , Microbioma Gastrointestinal/fisiologia , Rubus , Animais , Peso Corporal , Colo/metabolismo , Cumarínicos/sangue , Cumarínicos/metabolismo , Suplementos Nutricionais , Liofilização , Microbioma Gastrointestinal/genética , Hidroxibenzoatos/sangue , Hidroxibenzoatos/metabolismo , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Próstata/metabolismo , RNA Ribossômico 16S , Rubus/químicaRESUMO
Detection and identification of the in vivo metabolites of traditional Chinese medicine by untargeted profiling strategies are often confronted with severe interference from complex endogenous substances. Here we developed an integral approach, by combining untargeted data-dependent MS2 (dd-MS2) of Q-Orbitrap mass spectrometry and predictive multiple reaction monitoring-information dependent acquisition-enhanced product ion scan (pMRM-IDA-EPI) of triple quadrupole-linear ion trap (QTRAP) mass spectrometry, aiming to detect and identify more extensive metabolites in bio-samples. Ecliptae Herba (EH) is a widely consumed medicinal herb with the effects of nourishing liver/kidney, but its metabolites in vivo have not been fully elucidated. Firstly, after UHPLC separation on an HSS T3 column, chemical fingerprinting of 70% ethanolic extract of EH was performed by untargeted dd-MS2 in negative ion mode. We could characterize 41 compounds from EH, and 24 were detectable in the plasma of rats (prototypes) after oral administration of EH extract (1â¯g/kg). Secondly, using echinocystic acid (triterpene), wedelolactone (coumarin), and apigenin (flavonoid) as the different parent templates, an MRM list containing 150 predicted ion-pairs was established to enhance MS2 scan by pMRM-IDA-EPI, which enabled the primary identification of up to 200 metabolites. The biotransformations mainly involve oxidation, hydrogenation, methylation, glucuronidation, sulfonation etc. Thirdly, the rat plasma samples obtained after oral administration of three pure compounds (echinocystic acid, wedelolactone and apigenin) were analyzed to verify the reliability of metabolites identification, and 11, 4, and 10 metabolites were found individually. This is the first comprehensive research on the metabolism of EH in vivo.
Assuntos
Cumarínicos/sangue , Medicamentos de Ervas Chinesas , Eclipta/química , Flavonoides/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Biotransformação , Cromatografia Líquida de Alta Pressão , Cumarínicos/metabolismo , Cumarínicos/farmacocinética , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/metabolismo , Flavonoides/farmacocinética , Hidroxibenzoatos/sangue , Hidroxibenzoatos/metabolismo , Hidroxibenzoatos/farmacocinética , RatosRESUMO
To explore whether alcohol has an effect on the pharmacokinetic behavior of phenolic acids, the main bioactive constituents in red wine, a highly sensitive and simple ultra-fast liquid chromatography coupled with triple quadrupole mass spectrometry (UFLC-MS/MS) method was developed for simultaneous quantitation of eight phenolic acids in plasma samples. Plasma samples were extracted by liquid-liquid extraction and the chromatographic separation was achieved on a Zorbax SB-C18 column within 7.0 min. Results of the validated method revealed that all of the calibration curves displayed good linear regression (r > 0.99). The intra- and inter-day precisions of the analytes were <14.0% and accuracies ranged from -8.5 to 7.3%. The extraction recoveries of the analytes were from 71.2 to 110.2% and the matrix effects ranged from 86.2 to 105.5%. The stability of these compounds under various conditions satisfied the requirements of biological sample measurement. The method was successfully applied to a comparative pharmacokinetic study of phenolic acids in rat plasma. For gallic acid and gentisic acid, the parameters AUC0-t and AUC0-∞ increased remarkably (p < 0.05) after oral administration of red wine, which suggested that alcohol might enhance their absorption. This is the first report to compare the pharmacokinetic behavior of phenolic acids in red wine and dealcoholized red wine.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Hidroxibenzoatos/sangue , Hidroxibenzoatos/farmacocinética , Espectrometria de Massas em Tandem/métodos , Vinho , Animais , Estabilidade de Medicamentos , Hidroxibenzoatos/química , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos TestesRESUMO
This study has developed a reliable and precise high performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of five phenolic acids and four flavonoid glycosides in rat plasma after a single intravenous administration of Kudiezi injection (KI). Chromatographic separation was carried out on an Ultimate®XB-C18 column (4.6 × 100 mm, 3.5 µm) using a gradient elution program with a mobile phase consisting of water containing 0.5% acetic acid and acetonitrile at a flow rate of 0.6 mL/min. Detection was performed on a triple-quadrupole tandem mass spectrometry using multiple reaction monitoring in negative electrospray ionization mode. The calibration curves of all analytes showed good linearity (R² > 0.990). The results of selectivity, intra-day and inter-day precisions, extraction recoveries, matrix effects and stability were satisfactory. Pharmacokinetic parameters showed that luteolin-7-O-ß-d-gentiobioside, luteolin-7-O-ß-d-glucuronide, luteolin-7-O-ß-d-glucoside and apigenin-7-O-ß-d-glucuronide were eliminated quickly (0.07 h < t1/2 < 0.66 h), whereas 5-caffeoylquinic acid, caftaric acid, chlorogenic acid, 4-caffeoylquinic acid and caffeic acid were eliminated relatively slowly (2.22 h < t1/2 < 6.09 h) in rat blood. The pharmacokinetic results would be valuable to identify bioactive constituents, elucidate mechanisms of pharmacological actions or adverse drug reactions and guide the rational clinical use of KI.
Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Flavonoides/sangue , Glicosídeos/sangue , Hidroxibenzoatos/sangue , Administração Intravenosa , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/administração & dosagem , Masculino , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em TandemRESUMO
Several health promoting effects have been reported for maqui berry, rich in anthocyanins. Direct effects of anthocyanins as well as bioactive metabolites might be involved. Within the study, bioavailability of a proprietary standardized maqui berry extract Delphinol® was investigated based on two selected anthocyanins (delphinidin-3-O-glucoside (DS) + cyanidin-3-O-sambubioside (CS)) and two breakdown products (protocatechuic acid (PCA) + gallic acid (GA)) after a single-dose supplementation in humans. Pharmacokinetic parameters were calculated from individual concentration time curves. In all 12 subjects a significant increase was noted in plasma values of DG and CS after intake of maqui berry extract. Maximum concentration of DG was observed after 1.0 ± 0.3 h and CS after 2.0 ± 1.1 h. Within 8 h, concentrations nearly returned to baseline levels. The results confirm a fast uptake and metabolism of the two selected key substances. Additionally, the phenolic acids GA and PCA were observed as breakdown products of anthocyanins. In summary, the study clearly confirms the bioavailability of maqui berry extract and its specific anthocyanin compounds and related breakdown products in healthy subjects.
Assuntos
Suplementos Nutricionais , Frutas , Magnoliopsida , Extratos Vegetais/farmacocinética , Adulto , Antocianinas/sangue , Disponibilidade Biológica , Feminino , Ácido Gálico/sangue , Glucosídeos/sangue , Voluntários Saudáveis , Humanos , Hidroxibenzoatos/sangue , Masculino , Extratos Vegetais/sangue , Adulto JovemRESUMO
AIM: Co-metabolism between a human host and the gastrointestinal microbiota generates many small phenolic molecules such as 3-hydroxy-3-(3-hydroxyphenyl)propanoic acid (3,3-HPHPA), which are reported to be elevated in schizophrenia and autism. Characterization of these chemicals, however, has been limited by analytic challenges. METHODOLOGY/RESULTS: We applied HPLC to separate and quantify over 50 analytes, including multiple structural isomers of 3,3-HPHPA in human cerebrospinal fluid, serum and urine. Confirmation of identity was provided by NMR, by MS and other detection methods. The highly selective methods support rapid quantification of multiple metabolites and exhibit superior chromatographic behavior. CONCLUSION: An improved ultra-HPLC-MS/MS and structural approaches can accurately quantify 3,3-HPHPA and related analytes in human biological matrices.
Assuntos
Hidroxibenzoatos/metabolismo , Metabolômica/métodos , Cromatografia Líquida de Alta Pressão , Humanos , Hidroxibenzoatos/sangue , Hidroxibenzoatos/líquido cefalorraquidiano , Hidroxibenzoatos/urina , Isomerismo , Espectrometria de Massas em TandemRESUMO
In this study, for the first time a rapid, selective and highly sensitive method was developed for simultaneous determination of warfarin and mycophenolic acid using carbon paste electrode modified by ß-cyclodextrin/multi-walled carbon nanotubes/cobalt oxide nanoparticles (ß-CD/MWCNTs/Co3O4NPs/CPE). The oxidation peaks of desired drugs was separated enough using the constructed electrode. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were utilized for study the electrochemical response of the fabricated electrode and its surface modification was investigated by electrochemical impedance spectroscopy (EIS). Under optimal conditions, the adsorptive stripping voltammetric responses were linear in the concentration ranges 0.05-150⯵M and 0.5-200⯵M for WAR and MPA, respectively. The correlation coefficients were greater than 0.99. The limits of detection for WAR and MPA were 0.02 and 0.03⯵M. The fabricated electrode was applied for the simultaneous determination of WAR and MPA in urine and human serum samples with satisfactory results.
Assuntos
Técnicas Eletroquímicas , Hidroxibenzoatos , Varfarina , Adulto , Carbono/química , Eletrodos , Humanos , Hidroxibenzoatos/sangue , Hidroxibenzoatos/urina , Masculino , Varfarina/sangue , Varfarina/urinaRESUMO
Guan-Xin-Shu-Tong capsules are one of the well-known and first-line Chinese traditional herbal formula for treating coronary heart disease. A validated and sensitive method via ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was established to simultaneously determinate five phenolic acids and four diterpenoids in rats in order to investigate their pharmacokinetic profiles firstly. Analytes were extracted by ethyl acetate and determined via multiple reaction monitoring mode in both positive and negative ion modes. The values for limit of quantification were in range of 0.025-1.250ng/ml. Inter- and intra-day precisions were no more than 10.9% with accuracy of -11.0%-10.6%, meanwhile the stable and suitable extraction recoveries were also obtained. And finally such excellent method was used to compare the pharmacokinetics of nine compounds in normal and acute blood stasis rats after oral administration of Guan-Xin-Shu-Tong capsules.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Diterpenos/sangue , Medicamentos de Ervas Chinesas/administração & dosagem , Hidroxibenzoatos/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Diterpenos/química , Diterpenos/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Hidroxibenzoatos/química , Hidroxibenzoatos/farmacocinética , Modelos Lineares , Ratos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Mang-Guo-Zhi-Ke tablets (MGZKTs) is an effective Chinese patent medicine. It contains mango leaf extract as the main raw material and the antihistamine drug, chlorpheniramine maleate is included in the formulation. However, its pharmacokinetic effect is rarely reported. A highly sensitive, reliable and rapid high-throughput method using ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was used to simultaneously determine kaempferol, quercetin, mangiferin, p-hydroxybenzoic acid, gallic acid and chlorpheniramine maleate in rat plasma after oral administration of MGZKTs. The method was successfully developed and fully validated to investigate the pharmacokinetics of MGZKTs. Chloramphenicol and clarithromycin were used as internal standards (IS). A practicable protein precipitation procedure with methanol was adopted for sample preparation. The samples were separated on an Acquity UHPLC Syncronis C18 column (100 × 2.1 mm, 1.7 µm) using 0.1% formic acid-acetonitrile as the mobile phase. The flow rate was set at 0.4 mL/min. The obtained calibration curves were linear in the concentration range of ~1-1000 ng/mL for plasma (r > 0.99). Method validation results met the criteria reported in the US Food and Drug Administration guidelines. Quercetin, p-hydroxybenzoic acid and kaempferol were absorbed rapidly and reached the peak concentration between 0.16 and 0.25 h. This validated that the UHPLC-MS/MS method was successfully applied to study the pharmacokinetic parameters of the six compounds in rat plasma after oral administration of MGZKTs. This evidence will be useful for the clinical rational use of Mang-Guo-Zhi-Ke tablets.
Assuntos
Clorfeniramina/sangue , Medicamentos de Ervas Chinesas , Flavonóis/sangue , Hidroxibenzoatos/sangue , Xantonas/sangue , Administração Oral , Animais , Clorfeniramina/química , Clorfeniramina/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Flavonóis/química , Flavonóis/farmacocinética , Hidroxibenzoatos/química , Hidroxibenzoatos/farmacocinética , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem/métodos , Xantonas/química , Xantonas/farmacocinéticaRESUMO
Usnea longissima Ach. (Usnea) is used in pharmaceuticals, food and cosmetics. Evernic acid (EA), barbatic acid (BA), diffractaic acid (DA) and usnic acid (UA) are the most typical ingredients in U. longissima and exert a wide variety of biological functions. The study aimed to develop a sensitive method for simultaneous analysis of EA, BA, DA and UA in rat plasma and was applied to pharmacokinetic studies after consumption of UA and ethanol extract from U. longissima (UE). The samples were separated on a BEH C18 column by gradient elution with 0.5% formic acid in water and in methanol. The relative molecular masses of analytes were obtained in full-scan range from 50.0 to 750.0 m/z under negative ionization mode by UPLC-Q-Exactive Orbitrap MS. All validation parameters, such as lower limit of quantitation, linearity, specificity, precision, accuracy, extraction recovery, matrix effect and stability, were within acceptable ranges and the method was appropriate for biological specimen analysis. The pharmacokinetic results indicated that the absolute bioavailabilities of UA after oral administration of UA and UE reached 69.2 and 146.9%, respectively. Compared with UA in UE, the relative bioavailability of DA, BA and EA reached 103.7, 10.4 and 0.7% after oral administration of UE.
Assuntos
Anisóis/sangue , Benzofuranos/sangue , Hidroxibenzoatos/sangue , Ácidos Ftálicos/sangue , Animais , Anisóis/química , Anisóis/farmacocinética , Benzofuranos/química , Benzofuranos/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Hidroxibenzoatos/química , Hidroxibenzoatos/farmacocinética , Modelos Lineares , Masculino , Espectrometria de Massas/métodos , Ácidos Ftálicos/química , Ácidos Ftálicos/farmacocinética , Ratos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Plant phenols may accumulate in end-stage kidney disease. The effect of hemodialysis on their plasma concentration remains poorly determined. Contingent on concentration, health-promoting or noxious effects occur; therefore, we assessed plasma concentration in hemodialyzed patients. In total, 21 maintenance hemodialyzed patients with diuresis < 500 mL per day (with oliguria), nine hemodialyzed patients with diuresis ≥ 500 mL per day (without oliguria) and 31 healthy volunteers were included. Nine phenolic acids were identified with high-performance liquid chromatography and total polyphenol concentration was determined with the Folin-Ciocalteu method in pre- or post-hemodialysis plasma and pre- or intra-hemodialysis dialysate. The concentration of total polyphenols was 27% higher in pre-hemodialysis plasma than in that of controls (0.95 ± 0.18 mmol/L [P < 0.0001]). The concentration of total polyphenols was higher in patients with oliguria (1.01 ± 0.17) than in those without (0.84 ± 0.13 mmol/L), despite the former having more intense hemodialysis (Kt/V 1.29 ± 0.31 and 0.77 ± 0.25, respectively). Pre-hemodialysis phenolic acid concentration in patients undergoing dialysis exceeded reference values by 3 to 34 times (3-hydroxyphenylacetic acid and vanillic acid, respectively), from 0.69 (dihydrocaffeic acid) to 169.3 µmol/L (hippuric acid). The concentration of six phenolic acids (3-hydroxyhippuric, caffeic, dihydrocaffeic, hippuric, homovanillic, and vanillic acid) was 1.1 (homovanillic) to 11.3 (3-hydroxyhippuric) times higher in patients with oliguria than in those without. 4-hydroxyhippuric acid occurred more in the plasma of patients with oliguria than in those without oliguria. A single hemodialysis session decreased total polyphenol concentration by 16% and phenolic acids from 30% (caffeic) to 58% (vanillic and 3-hydroxyphenylacetic acid) and these compounds appeared in the dialysate. The percentage decrease (Δ%) of creatinine concentration correlated with the Δ% of total polyphenols and five phenolic acids (3-hydroxyphenylacetic, dihydrocaffeic, hippuric, homovanillic, and vanillic acid). Urea Δ% and Kt/V correlated only with the Δ% of homovanilic acid. The results demonstrate that phenols accumulate variably in hemodialyzed patients and are differently eliminated during hemodialysis. Residual renal function ensures a lower concentration of plasma phenols.
Assuntos
Hidroxibenzoatos/sangue , Falência Renal Crônica/terapia , Fenóis/sangue , Diálise Renal/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Creatinina/metabolismo , Soluções para Diálise/química , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Oligúria/terapiaRESUMO
SCOPE: Understanding the metabolic fate of polyphenols from plant foods can aid in developing dietary recommendations that maximize their health benefits. Wild blueberries (WBB) provide a distinctive composition of dietary anthocyanins and chlorogenic acid (CGA). METHODS AND RESULTS: This is a single blind, randomized, two-arm crossover controlled study. Human subjects ingested a WBB beverage (25 g freeze dried WBB powder) or placebo beverage with a meal and plasma was collected over 24 h. Anthocyanins, CGA and their metabolites were characterized and quantified in beverages and in plasma using targeted and non-targeted mass analyses. Bioavailability of WBB anthocyanins and 3-CGA was 1.1 and 0.2%, respectively. Parent anthocyanins and 3-CGA peaked ≈2 h post ingestion, while phase II metabolites, including glucuronide conjugates of peonidin, delphinidin, cyanidin and petunidin peaked ≈ 2.6, 6.3, 7 and 8.8 h, respectively. Phenolic acids (metabolites) peaked between 0.5 and 24 h. Biphasic responses were evident suggesting preferential enterohepatic recycling for some compounds. CONCLUSION: The data indicate bioavailability of early and late phase WBB metabolites peaking at different times during the 24 h period, which may be important for maximizing their biological activity.