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Extracts from medicinal plants are widely used in the treatment and prevention of different diseases. Micromeria frivaldszkyana is a Balkan endemic species with reported antioxidant and antimicrobial characteristics; however, its phytochemical composition is not well defined. Here, we examined the metabolome of M. frivaldszkyana by chromatography–mass spectrometry (GC-MS), ultra-performance liquid chromatography–mass spectrometry (UPLC-MS-MS), and inductively coupled plasma mass spectrometry (ICP-MS). Amino acids, organic acids, sugars, and sugar alcohols were the primary metabolites with the highest levels in the plant extract. Detailed analysis of the sugar content identified high levels of sucrose, glucose, mannose, and fructose. Lipids are primary plant metabolites, and the analysis revealed triacylglycerols as the most abundant lipid group. Potassium (K), magnesium (Mg), zinc (Zn), and calcium (Ca) were the elements with the highest content. The results showed linarin, 3-caffeoil-quinic acid, and rosmarinic acid, as well as a number of polyphenols, as the most abundant secondary metabolites. Among the flavonoids and polyphenols with a high presence were eupatorin, kaempferol, and apigenin—compounds widely known for their bioactive properties. Further, the acute toxicity and potential anti-inflammatory activity of the methanolic extract were evaluated in Wistar rats. No toxic effects were registered after a single oral application of the extract in doses of between 200 and 5000 mg/kg bw. A fourteen-day pre-treatment with methanolic extract of M. frivaldszkyana in doses of 250, 400, and 500 mg/kg bw induced anti-inflammatory activity in the 1st, 2nd, and 3rd hours after carrageenan injection in a model of rat paw edema. This effect was also present in the 4th hour only in the group treated with a dose of 500 mg/kg. In conclusion, M. frivaldszkyana extract is particularly rich in linarin, rosmarinic acid, and flavonoids (eupatorin, kaempferol, and apigenin). Its methanolic extract induced no toxicity in male Wistar rats after oral application in doses of up to 5000 mg/kg bw. Additionally, treatment with the methanolic extract for 14 days revealed anti-inflammatory potential in a model of rat paw edema on the 1st, 2nd, and 3rd hours after the carrageenan injection. These results show the anti-inflammatory potential of the plant, which might be considered for further exploration and eventual application as a phytotherapeutic agent. [ABSTRACT FROM AUTHOR]

Excessive weight and obesity are the leading risk factors for the development of chronic diseases, including diabetes. Metformin is capable of significantly improving coexisting complications of diabetes. We used a metabolomics approach to examine the effects of metformin administration on lean and obese (fa/fa) Zucker rats. After 1 week of acclimation, twenty-eight 5-week-old female lean and obese rats were randomly assigned to and maintained in the following four groups (seven rats/group) for 10 weeks: (1) lean control (LC); (2) obese control (OC); (3) lean metformin (LM); and (4) obese metformin (OM). At the end of 10 weeks, serum was collected and analyzed using HPLC with electrochemical detection, HPLC with UV detection, and liquid chromatography mass spectrometry. We selected 50 metabolites' peaks that were shared by all four groups of rats. Peak heights, as a defining factor, generally decreased in metformin-treated lean rats vs. untreated lean controls (3 LM:16 LC). Peak heights generally increased in metformin-treated obese rats vs. untreated obese controls (14 OM:5 OC). Overall, individual peaks were distributed as 11 that represented only lean rats, 11 that represented only obese rats, and 8 that were common among both lean and obese rats. In future studies, we will use a targeted metabolomics approach to identify those metabolites, map them to biochemical pathways and create a list of biomarkers. In summary, the current study contributed to a better understanding of the basic metabolic changes of lean and obese rats and demonstrated that both obesity and metformin make a significant impact on the metabolome of Zucker rats. [ABSTRACT FROM AUTHOR]

LE300 is a novel dopamine receptor antagonist used to treat cocaine addiction. In the current study, a sensitive and fast liquid chromatography–tandem mass spectrometry (LC-MS/MS) has been established and validated for the simultaneous analysis of LE300 and its N-methyl metabolite, MLE300, in rat plasma with an application in a pharmacokinetic study. The chromatographic elution of LE300, MLE300, and Ponatinib (IS, internal standard), was carried out on a 50 mm C18 analytical column (ID: 2.1 mm and particle size: 1.8 μm) maintained at 22 ± 2 °C. The run time was 5 min at a flow rate of 0.3 mL/min. The mobile phase consisted of 42% aqueous solvent (10 mM ammonium formate, pH: 4.2 with formic acid) and 58% organic solvent (acetonitrile). Plasma samples were pretreated using protein precipitation with acetonitrile. The electrospray ionization (ESI) source was used to generate an ion-utilizing positive mode. A multiple reaction monitoring mass analyzer mode was utilized for the quantification of analytes. The linearity of the calibration curves in rat plasma ranged from 1 to 200 ng/mL (r2 = 0.9997) and from 2 to 200 ng/mL (r2 = 0.9984) for LE300 and MLE300, respectively. The lower limits of detection (LLOD) were 0.3 ng/mL and 0.7 ng/mL in rat plasma for LE300 and MLE300, respectively. Accuracy (RE%) ranged from −1.71% to −0.07% and −4.18% to −1.48% (inter-day), and from −3.3% to −1.47% and −4.89% to −2.15% (intra-day) for LE300 and MLE300, respectively. The precision (RSD%) was less than 2.43% and 1.77% for the inter-day, and 2.77% and 1.73% for intra-day of LE300 and MLE300, respectively. These results are in agreement with FDA guidelines. The developed LC-MS/MS method was applied in a pharmacokinetic study in Wistar rats. Tmax and Cmax were 2 h and 151.12 ± 12.5 ng/mL for LE300, and 3 h and 170.4 ± 23.3 ng/mL for MLE300. [ABSTRACT FROM AUTHOR]

Background: Since most of the modern human population has no anti-smallpox immunity, it is extremely important to develop and implement effective drugs for the treatment of smallpox and other orthopoxvirus infections. The objective of this study is to determine the main characteristics of the chemical substance NIOCH-14 and its safety and bioavailability in the body of laboratory animals. Methods: The safety of NIOCH-14 upon single- or multiple-dose intragastric administration was assessed according to its effect on the main hematological and pathomorphological parameters of laboratory mice and rats. In order to evaluate the pharmacokinetic parameters of NIOCH-14 administered orally, a concentration of ST-246, the active metabolite of NIOCH-14, in mouse blood and organs was determined by tandem mass spectrometry and liquid chromatography. Results: The intragastric administration of NIOCH-14 at a dose of 5 g/kg body weight caused neither death nor signs of intoxication in mice. The intragastric administration of NIOCH-14 to mice and rats at doses of 50 and 150 µg/g body weight either as a single dose or once daily during 30 days did not cause animal death or critical changes in hematological parameters and the microstructure of internal organs. The tissue availability of NIOCH-14 administered orally to the mice at a dose of 50 µg/g body weight, which was calculated according to concentrations of its active metabolite ST-246 for the lungs, liver, kidney, brain, and spleen, was 100, 69.6, 63.3, 26.8 and 20.3%, respectively. The absolute bioavailability of the NIOCH-14 administered orally to mice at a dose of 50 µg/g body weight was 22.8%. Conclusion: Along with the previously determined efficacy against orthopoxviruses, including the smallpox virus, the substance NIOCH-14 was shown to be safe and bioavailable in laboratory animal experiments. [ABSTRACT FROM AUTHOR]

Synthetic cathinones are one important group amongst new psychoactive substances (NPS) and limited information is available regarding their toxicokinetics and -dynamics. Over the past few years, nontargeted toxicometabolomics has been increasingly used to study compound-related effects of NPS to identify important exogenous and endogenous biomarkers. In this study, the effects of the synthetic cathinone PCYP (2-cyclohexyl-1-phenyl-2-(1-pyrrolidinyl)-ethanone) on in vitro and in vivo metabolomes were investigated. Pooled human-liver microsomes and blood and urine of male Wistar rats were used to generate in vitro and in vivo data, respectively. Samples were analyzed by liquid chromatography and high-resolution mass spectrometry using an untargeted metabolomics workflow. Statistical evaluation was performed using univariate and multivariate statistics. In total, sixteen phase I and one phase II metabolite of PCYP could be identified as exogenous biomarkers. Five endogenous biomarkers (e.g., adenosine and metabolites of tryptophan metabolism) related to PCYP intake could be identified in rat samples. The present data on the exogenous biomarker of PCYP are crucial for setting up analytical screening procedures. The data on the endogenous biomarker are important for further studies to better understand the physiological changes associated with cathinone abuse but may also serve in the future as additional markers for an intake. [ABSTRACT FROM AUTHOR]

Background: Systemic arterial hypertension, which is associated with an increased risk of cardiovascular disease(CVD), is the most significant modifiable risk factor for mortality and morbidity worldwide. WHO has recognized Unanipathy as an alternate system of medicine. The aim of the present study is to investigate the anti-hypertensive activity of some selected unani formulations using L-NAME model. Method: Group I or hypertensive control group: L-NAME administered for 7 days and left for the next 7 days; Group II or KASgroup: L-NAME administered (i.p) for 7 days and L-NAME + KAS (1000 mg/kg b.w) for the next 7 days; Group III or DMM group: L-NAME administered (i.p) for 7 days and L-NAME + DMM (2000 mg/kg b.w) for the next 7 days; Group IV or MSR group: L-NAME administered (i.p) for 7 days and L-NAME + MSR (300 mg/kg b.w) for the next 7 days; Group V or HJ group: L-NAME administered (i.p) for 7 days and L-NAME + HJ (113 mg/kg b.w) for the next 7 days; Group VI or KGS group: L-NAME administered (i.p) for 7 days and L-NAME +KGS (2000 mg/kg b.w) for the next 7 days. Non-invasive systolic blood pressure and RR-interval (ECG) was measured. Plasma was investigated forsodium, potassium, nitrite, ANP, adrenaline, noradrenaline and aldosterone on day 0, 7 and 14 using LC-MS/MS. Result: Treatment showed a non-significant lowreduction in SBP (systolic blood pressure) of KAS, MSR and HJ while that of DMM was quite significant (p < 0.05), but in the case of KGS, SBP increased. DMM on day 14 significantly (p < 0.05) reduced plasma nitrite while no significant plasma Na+ was noted. In the case of both DMM and KGS, potassium increased significantly (p < 0.05) on day 14. No significant changes in plasma ANP and aldosterone was observed against DMM and KGS while blood levels of adrenaline and noradrenaline significantly (p < 0.05) changed. No significant change in body weight was found. Conclusions: L-NAME KAS, MSR and HJ showed no change in SBP while DMM showed a significant reduction in SBP with decreased plasma nitrite. Probably, DMM may have anti-hypertensive activity mediated through NO inhibition while KGS may involve central sympathomimetic action. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD) showed anticonvulsant action in several preclinical models and is currently approved by regulatory agencies to treat childhood epilepsy syndromes. However, CBD treatment has limited benefits, and its long-term effects on cognition are not fully understood yet. This study aimed to examine the impact of long-term CBD treatment in the pentylenetetrazole (PTZ)-kindling model of epilepsy. Adult male Wistar rats (N = 24) received PTZ (35 mg/kg intraperitoneally) every other day until two consecutive generalized seizures occurred. CBD (60 mg/kg body weight) was administered daily by the oral route until the kindled state was achieved (n = 12). To confirm that the formulation and administration techniques were not of concern, liquid chromatography–mass spectrometry was performed to test the brain penetration of the CBD formula. As a result of CBD treatment, a lower mortality rate and significantly prolonged generalized seizure latency (925.3 ± 120.0 vs. 550.1 ± 69.62 s) were observed, while the frequency and duration of generalized seizures were not influenced. The CBD-treated group showed a significant decrease in vertical exploration in the open field test and a significant decrease in the discrimination index in the novel object recognition (NOR) test (−0.01 ± 0.17 vs. 0.57 ± 0.15, p = 0.04). The observed behavioral characteristics may be connected to the decreased thickness of the stratum pyramidale or the decreased astrogliosis observed in the hippocampus. In conclusion, CBD treatment did not prevent kindling, nor did it affect seizure frequency or duration. However, it did increase the latency to the first seizure and decreased the prolonged status epilepticus-related mortality in PTZ-kindled rats. The cognitive impairment observed in the NOR test may be related to the high dose used in this study, which may warrant further investigation. [ABSTRACT FROM AUTHOR]

Wistar and Sprague Dawley are the most common strains of rat used in pharmaceutical research and are used interchangeably in pre-clinical drug development. No studies have assessed whether Wistar and Sprague Dawley rats are equivalent in the gastrointestinal factors that influence oral drug absorption, specifically in relation to intestinal transporters. Enzyme-linked immunosorbent assay (ELISA) and liquid chromatography–tandem mass spectrometry (LC-MS/MS) are two reliable methods for quantifying intestinal protein levels with their own distinct advantages and limitations. In this study, P-glycoprotein (P-gp), a key efflux transporter, was quantified using ELISA and LC-MS/MS along the complete intestinal tract of male and female Wistar and Sprague Dawley rats. This work presents that Sprague Dawley rats have innately higher baseline P-gp expression than Wistar rats. Significant sex differences in P-gp expression were identified in the jejunum, ileum and colon between male and female Wistar rats using both techniques, with males exhibiting higher P-gp levels. Sprague Dawley rats showed no sex differences in P-gp expression through ELISA and LC-MS/MS. Both methods demonstrated similar trends for P-gp quantification, but ELISA could offer faster data acquisition. Our findings report significant sex differences between the strains and highlight that Wistar and Sprague Dawley rats are not equivalent in their P-gp expression. As humans exhibit distinct sex differences in intestinal P-gp levels, Wistar rats may therefore be a more suitable pre-clinical animal strain to model oral drug absorption of P-gp substrates in male and female subjects. [ABSTRACT FROM AUTHOR]

Aging is an inevitable condition leading to health deterioration and death. Regular physical exercise can moderate the metabolic phenotype changes of aging. However, only a small number of metabolomics-based studies provide data on the effect of exercise along with aging. Here, urine and whole blood samples fromWistar rats were analyzed in a longitudinal study to explore metabolic alterations due to exercise and aging. The study comprised three different programs of exercises, including a life-long protocol which started at the age of 5 months and ended at the age of 21 months. An acute exercise session was also evaluated. Urine and whole blood samples were collected at different time points and were analyzed by LC-MS/MS (Liquid Chromatography-tandem Mass Spectrometry). Based on their metabolic profiles, samples from trained and sedentary rats were differentiated. The impact on the metabolome was found to depend on the length of exercise period with acute exercise also showing significant changes. Metabolic alterations due to aging were equally pronounced in sedentary and trained rats in both urine and blood analyzed samples. [ABSTRACT FROM AUTHOR]

In the present investigation, we identified the phytochemical constituents of total oligomeric flavonoid fraction (TOF) of Cyperus rotundus by LC–ESI-MS/MS and also demonstrated its antihemolytic effects against 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) induced hemolysis of rat erythrocytes. Our results of TOF extract exhibited DPPH, metal chelating, ABTS, NO and hydroxyl radical scavenging activities with an IC 50 values of 23.72 ± 1.6, 52.45 ± 2.88, 9.8 ± 0.42, 6.5 ± 0.33 and 120 ± 6.83 μg/ml respectively, whereas total antioxidant and reducing power activities were 194 ± 12.5 μg GAE/mg extract and 145 ± 8.3 μg AAE/mg extract. The extract showed potent inhibitory activity against AAPH induced plasmid DNA damage, protein oxidation and lipid peroxidation. The TOF extract mitigates AAPH induced hemolysis and exhibits ∼50% antihemolytic activity. TOF pretreatment also preserved morphology of erythrocytes as observed and measured by light microscope and atomic force microscope analysis. Furthermore, the TOF fraction effectively inhibited AAPH induced LDH release, ROS generation and lipid peroxidation. Taken together, our data demonstrate the antihemolytic activity of C. rotundus against AAPH induced oxidative stress of erythrocytes, and was associated with the decrease in oxidative stress, cellular damage and protection of macromolecules. In conclusion, the effects might be correlated with high content of flavonoids and polyphenols identified in C. rotundus . This suggests the clinical application of TOF fraction of C. rotundus against ROS induced cell death. [ABSTRACT FROM AUTHOR]

Caudatin is a potential antitumor agent isolated from the traditional Chinese medicine "baishouwu", which was the root tuber of Cynanchum auriculatum Royle ex Wight. In our previous studies, caudatin showed selectivity on human hepatoma cell line SMMC7721 among several different tumor cell lines, and further in vivo tests validated the inhibitory action of caudatin against hepatic cancer using an H22 solid tumor model in mice, but to our knowledge, the biopharmaceutical properties of caudatin are largely unknown. In this study, a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of caudatin in rat plasma and tissues, which kept the run time to detect one sample within 4 min, was developed and validated. Pharmacokinetics and tissue distribution studies of caudatin in conventional rats and hepatocellular carcinoma (HCC) model rats were then conducted for the first time. Statistically significant differences were observed between conventional rats and diethylnitrosamine (DEN)-induced HCC rats with respect to pharmacokinetic parameters, including maximum concentration (Cmax), time to reach Cmax (Tmax), half-life (t1/2), area under the concentration-time curve (AUC0-t, AUC0-∞), mean residence time (MRT0-t and MRT0-∞), and oral clearance (CL/F). Increased exposures of caudatin were found in the plasma and livers of HCC model rats, which would be helpful for a better understanding of pharmacological effect of caudatin in treating HCC disease. [ABSTRACT FROM AUTHOR]

A rapid, sensitive and selective liquid chromatography/tandem mass spectrometry method (LC-MS/MS) was developed and validated for determination of dehydrocorydaline (DHC) in rat plasma using nitidine chloride as an internal standard. The analytes were solid-phase extracted and eluted on a C18 chromatography column using a mobile phase of acetonitrile and water (containing 0.8% formic acid and 10 mM ammonium acetate) (28:72, v/v). Detection was performed using positive ion electrospray ionization in multiple reaction monitoring modes. The assay was linear over the concentration range 0.625-250 ng/mL with a quantification limit of 0.625 ng/mL. The precision was <13.7%, the accuracy >93.1%, and extraction recovery ranged from 92.1% to 107%. The validated method was successfully applied to the pharmacokinetics and excretion study of DHC in rat plasma after oral administration of pure DHC and an effective fraction of Corydalis yanhusuo (EFY). The pharmacokinetic parameters showed that DHC from EFY was absorbed more rapidly and eliminated more slowly than pure DHC. The result suggests that the differences might be due to the presence of P-glycoprotein (P-gp) inhibitors and that other alkaloids co-existing in the EFY may compete with DHC for transportation by P-gp, metabolization by P450, and binding to plasma proteins. [ABSTRACT FROM AUTHOR]

Di(2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in various industrial and household plastic products, ensuring widespread human exposures. Its routine detection in human bio-fluids and the propensity of its monoester metabolite to activate peroxisome proliferator activated receptor-α (PPARα) and perturb lipid metabolism implicate it as a metabolic disrupter. In this study we evaluated the effects of DEHP exposure on hepatic levels of free CoA and various CoA esters, while also confirming the metabolic activation to CoA esters and partial β-oxidation of a DEHP metabolite (2-ethyhexanol). Male Wistar rats were exposed via diet to 2% (w/w) DEHP for fourteen-days, following which hepatic levels of free CoA and various CoA esters were identified using liquid chromatography-mass spectrometry. DEHP exposed rats showed significantly elevated free CoA and increased levels of physiological, DEHP-derived and unidentified CoA esters. The physiological CoA ester of malonyl-CoA and DEHP-derived CoA ester of 3-keto-2-ethylhexanoyl-CoA were the most highly elevated, at eighteen- and ninety eight-times respectively. We also detected sixteen unidentified CoA esters which may be derivative of DEHP metabolism or induction of other intermediary metabolism metabolites. Our results demonstrate that DEHP is a metabolic disrupter which affects production and sequestration of CoA, an essential cofactor of oxidative and biosynthetic reactions. [ABSTRACT FROM AUTHOR]

A sensitive and accurate ultra-performance liquid chromatography coupled with triple quadrupole mass (UPLC-MS/MS) method was developed for the determination of quercetin-3-O-β-D-glucopyranoside-(4→1)-α-L-rhamnoside (QGR) in rat plasma using rutin as internal standard. Chromatographic separation was achieved on a Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with a gradient elution of acetonitrile and 0.10% formic acid (v/v) at a flow rate of 0.4 mL/min. QGR and rutin were detected using electrospray negative ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The method demonstrated good linearity and did not show any endogenous interference with the QGR and rutin peaks. This method was successfully applied to a pharmacokinetic study of QGR in rats after intravenous (20 mg/kg) and oral (40 mg/kg) administration, and the results showed that the compound was poorly absorbed, with an absolute bioavailability of approximately 3.41%. [ABSTRACT FROM AUTHOR]

A rapid sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for determination of timosaponin AIII (TA-III) in rat plasma, using ginsenoside Re as an internal standard (IS). TA-III and the IS were detected in MRM mode with a negative ionization electrospray mass spectrometer. The calibration curves were linear over the concentration ranges from 11.14 to 1114 ng/mL and the lower limit of quantification (LLOQ) was 11.14 ng/mL. Intra-day and inter-day precisions (RSD) were within 10%, and accuracy ranged from 6.4% to 9.1%. The extraction recovery at three concentrations ranged from 92.3% to 95.5%. The validated method was successfully applied to monitor the concentrations of TA-III in rat plasma after intragastric administration. The best fit pharmacokinetic model to estimate the pharmacokinetic parameters was a single compartment model with weight of 1/x2 for oral administration groups of rats for TA-III. [ABSTRACT FROM AUTHOR]

The rat is one of the most commonly used animal models in pre-clinical studies. Limited information between the sexes and the effect of food consumption on the gastrointestinal (GI) physiology, however, is acknowledged or understood. This study aimed to investigate the potential sex differences and effect of food intake on the intestinal luminal fluid and the efflux membrane transporter P-glycoprotein (P-gp) along the intestinal tract of male and female Wistar rats. To characterise the intestinal luminal fluids, pH, surface tension, buffer capacity and osmolality were measured. Absolute P-gp expression along the intestinal tract was quantified via liquid chromatography-tandem mass spectrometry (LC-MS/MS). In general, the characteristics of the luminal fluids were similar in male and female rats along the GI tract. In fasted male rats, the absolute P-gp expression gradually increased from the duodenum to ileum but decreased in the colon. A significant sex difference (p < 0.05) was identified in the jejunum where P-gp expression in males was 83% higher than in females. Similarly, ileal P-gp expression in male rats was approximately 58% higher than that of their female counterparts. Conversely, following food intake, a significant sex difference (p < 0.05) in P-gp expression was found but in a contrasting trend. Fed female rats expressed much higher P-gp levels than male rats with an increase of 77% and 34% in the jejunum and ileum, respectively. A deeper understanding of the effects of sex and food intake on the absorption of P-gp substrates can lead to an improved translation from pre-clinical animal studies into human pharmacokinetic studies. [ABSTRACT FROM AUTHOR]

The metabolic and pharmacokinetic studies on complanatuside, a quality marker of a Chinese materia medicatonic, Semen Astragali Complanati, were carried out. The UHPLC-Q-TOF/MS (ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry) method was applied to identify the metabolites of complanatuside in rat plasma, bile, stool, and urine after oral administration at the dosage of 72 mg/kg. Up to 34 metabolites (parent, 2 metabolites of the parent drug, and 31 metabolites of the degradation products) were observed, including processes of demethylation, hydroxylation, glucuronidation, sulfonation, and dehydration. The results indicated glucuronidation and sulfonation as major metabolic pathways of complanatuside in vivo. Meanwhile, a HPLC-MS method to quantify complanatuside and its two major metabolites—rhamnocitrin 3-O-β-glc and rhamnocitrin—in rat plasma for the pharmacokinetic analysis was developed and validated. The Tmax (time to reach the maximum drug concentration) of the above three compounds were 1 h, 3 h, and 5.3 h, respectively, while the Cmax (maximum plasma concentrations)were 119.15 ng/mL, 111.64 ng/mL, and 1122.18 ng/mL, and AUC(0-t) (area under the plasma concentration-time curve) was 143.52 µg/L·h, 381.73 µg/L·h, and 6540.14 µg/L·h, accordingly. The pharmacokinetic characteristics of complanatuside and its two metabolites suggested that complanatuside rapidly metabolized in vivo, while its metabolites—rhamnocitrin—was the main existent form in rat plasma after oral administration. The results of intracorporal processes, existing forms, and pharmacokinetic characteristics of complanatuside in rats supported its low bioavailability. [ABSTRACT FROM AUTHOR]

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-β-d-gentiobioside, luteolin-7-O-β-d-glucuronide, luteolin-7-O-β-d-glucoside and apigenin-7-O-β-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. [ABSTRACT FROM AUTHOR]

The herbal formula Yin-Chen-Hao-Tang has been reported to have anti-fibrosis properties. The aim of this study was to reveal the pharmacokinetic characteristics of bioactive compounds in this herbal formula. A new high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of scoparone, geniposide and rhein in rat plasma. A pharmaceutical herbal powder was administered to rats at doses of 1 g/kg and 3 g/kg orally. The method showed excellent linearity (r2 > 0.999) and validation was successfully conducted for the pharmacokinetic study. The results show that the Cmax values and areas under the curve of scoparone, geniposide and rhein were higher and not proportional to the dose in rat plasma, while the Tmax and half-life values were consistent in the group that received 1 g/kg. The clearance of the higher dose (3 g/kg) did not decrease proportionally to that of the low dose. The results showed the nonlinear pharmacokinetic properties of scoparone, geniposide and rhein in Yin-Chen-Hao-Tang that suggested possible accumulation of bioactive compounds through oral administration. This pharmacokinetic study reveals that an increased dose of this herbal formula would largely increase the maximum concentration and bioavailability of scoparone, geniposide and rhein. [ABSTRACT FROM AUTHOR]

Xiaoyao Powder (XYP), a common Chinese medicine, comprises eight traditional Chinese herbs and has been widely used clinically to treat liver damage and mental disorders. An ultra-performance liquid chromatography–tandem mass spectrometry method was developed to investigate the pharmacokinetics of 14 compounds (albiflorin, paeoniflorin, ferulic acid, senkyunolide I, quercetin, isoliquiritigenin, atractylenolide III, ligustilide, atractylenolide II, liquiritin, liquiritigenin, saikosaponin c, glycyrrhizic acid, and saikosaponin a) in XYP. Naringenin was used as the internal standard. The compounds were separated using an ACQUITY UPLCTM BEH C18 column (1.7 μm, 50 × 2.1 mm) with a mobile phase consisting of acetonitrile and 0.1% formic acid in water at a flow rate of 0.3 mL/min. Detection was performed on a triple-quadrupole tandem mass spectrometer using multiple reaction monitoring and an electrospray ionization source in both positive and negative ionization modes. All calibration curves exhibited good linearity (r2 > 0.9974) over the measured ranges. The intra- and inter-day precisions were within 12%, and the accuracy ranged from 89.93% to 106.64%. Extraction recovery and matrix effect results were satisfactory. The method was successfully applied in a pharmacokinetic study of the 14 compounds in rat plasma after the oral administration of XYP. [ABSTRACT FROM AUTHOR]

Rumex acetosa (R. acetosa) has been used in folk remedies for gastrointestinal disorders and cutaneous diseases. Rumex species, in particular, contain abundant anthraquinones. Anthraquinone glycosides and aglycones show different bioactive effects. However, information on the pharmacokinetics of anthraquinone glycosides is limited, and methods to quantify anthraquinone glycosides in plasma are rarely available. A simple and sensitive liquid chromatography-tandem mass spectrometric bioanalytical method for the simultaneous determination of both anthraquinone glycosides and their aglycones, including emodin, emodin-8-O-β-d-glucoside, chrysophanol, chrysophanol-8-O-β-d-glucoside, physcion, and physcion-8-O-β-d-glucoside , in a low volume of rat plasma (20 µL) was established. A simple and rapid sample preparation was employed using methanol as a precipitating agent with appropriate sensitivity. Chromatographic separation was performed on HPLC by using a biphenyl column with a gradient elution using 2 mM ammonium formate (pH 6) in water and 2 mM ammonium formate (pH 6) in methanol within a run time of 13 min. The anthraquinones were detected on triple-quadrupole mass spectrometer in negative ionization mode using multiple-reaction monitoring. The method was validated in terms of selectivity, linearity, accuracy, precision, recovery, and stability. The values of the lower limit of quantitation of anthraquinones were 1–20 ng/mL. The intra-batch and inter-batch accuracies were 96.7–111.9% and the precision was within the acceptable limits. The method was applied to a pharmacokinetic study after oral administration of R. acetosa 70% ethanol extract to rats at a dose of 2 g/kg. [ABSTRACT FROM AUTHOR]