scholarly journals Herb-Drug Interaction: Application of a UPLC-MS/MS Method to Determine the Effect of Polygonum capitatum Extract on the Tissue Distribution and Excretion of Levofloxacin in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Li Yuan ◽  
Hao Chen ◽  
Xue Ma ◽  
Jie Pan ◽  
Zi-Peng Gong ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Tissue Distribution ◽  
Urinary System ◽  
Limit Of Quantification ◽  
Chinese Herbal ◽  
Combined Application ◽  
Liquid Chromatography Tandem Mass ◽  
Tandem Mass Spectroscopy ◽  
Cumulative Excretion

Polygonum capitatum has unique curative effects on the urinary system. In fact, many Polygonum capitatum-based preparations are currently used in the clinic. In China, the combination of levofloxacin (LVFX) with a Chinese herbal preparation derived from Polygonum capitatum has been used for the clinical treatment of urinary system diseases, which can improve the curative effects and reduce the side effects of LVFX. However, the herb-drug interaction (HDI) between these drugs has not been reported and the effect of Polygonum capitatum on the in vivo process of LVFX is unclear. In this article, a sensitive ultraperformance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) method was developed to evaluate the effects of the combined application of LVFX and the Polygonum capitatum extract on tissue distribution and excretion. Thereafter, the method was validated for selectivity, accuracy, precision, linearity, lower limit of quantification (LLOQ), dilution integrity, recovery, and matrix effect. Based on tissue distribution, LVFX could diffuse into all of the tested tissues, with significant differences in the content of each tissue between the coadministration group and single administration group. At 48 h after the combination was orally administered, the urinary cumulative excretion of LVFX decreased from 20.69% to 11.84% while its fecal cumulative excretion decreased from 26.08% to 13.28%. Our results suggest that a drug interaction exists between the two drugs in the process of distribution and excretion. This study provides important experimental evidence for further studies on the clinical efficacy and mechanism of the Polygonum capitatum extract and LVFX.

scholarly journals High-Performance Liquid Chromatography-Tandem Mass Spectrometry for Buprenorphine Evaluation in Plasma—Application to Pharmacokinetic Studies in Rabbits

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 437
Author(s):  
Marta Tikhomirov ◽  
Błażej Poźniak ◽  
Tomasz Śniegocki
Keyword(s):  
High Performance ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Studies ◽  
Limit Of Quantification ◽  
Reliable Determination ◽  
Main Challenge ◽  
Analytical Protocol ◽  
Liquid Chromatography Tandem Mass ◽  
Cost Efficient

The precise and reliable determination of buprenorphine concentration is fundamental in certain medical or research applications, particularly in pharmacokinetic studies of this opioid. The main challenge is, however, the development of an analytical method that is sensitive enough, as the detected in vivo concentrations often fall in very low ranges. Thus, in this study we aimed at developing a sensitive, repeatable, cost-efficient, and easy HPLC analytical protocol for buprenorphine in rabbit plasma. In order to obtain this, the HPLC-MS2 system was used to elaborate and validate the method for samples purified with liquid-liquid extraction. Fragment ions 468.6→396.2 and 468.6→414.2 were monitored, and the method resulted in a high repeatability and reproducibility and a limit of quantification of 0.25 µg/L with a recovery of 98.7–109.0%. The method was linear in a range of 0.25–2000 µg/L. The suitability of the analytical procedure was tested in rabbits in a pilot pharmacokinetic study, and it was revealed that the method was suitable for comprehensively describing the pharmacokinetic profile after buprenorphine intravenous administration at a dose of 300 µg/kg. Thus, the method suitability for pharmacokinetic application was confirmed by both the good validation results of the method and successful in vivo tests in rabbits.

scholarly journals Analysis of the Carry-Over of Ochratoxin A from Feed to Milk, Blood, Urine, and Different Tissues of Dairy Cows Based on the Establishment of a Reliable LC-MS/MS Method

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2823 ◽  
Author(s):  
Zhiqi Zhang ◽  
Zhichen Fan ◽  
Dongxia Nie ◽  
Zhihui Zhao ◽  
Zheng Han
Keyword(s):  
Dairy Cows ◽  
Ochratoxin A ◽  
Limit Of Quantification ◽  
Fresh Milk ◽  
Liquid Chromatography Tandem Mass ◽  
Ochratoxin Α ◽  
Carry Over ◽  
First Time ◽  
Different Tissues

A rapid and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous determination of ochratoxin A (OTA) and its metabolite ochratoxin α (OTα), for the first time, in dairy cow plasma, milk, urine, heart, liver, spleen, lung, and kidney. The established method was extensively validated by determining the linearity (R2 ≥ 0.990), sensitivity (lower limit of quantification, 0.1–0.2 ng mL−1), recovery (75.3–114.1%), precision (RSD ≤ 13.6%), and stability (≥83.0%). Based on the methodological advances, the carry-over of OTA was subsequently studied after oral administration of 30 μg/kg body weight OTA to dairy cows. As revealed, OTA and OTα were detected in urine, with maximal concentrations of 1.8 ng mL−1 and 324.6 ng mL−1, respectively, but not in milk, plasma, or different tissues, verifying the protection effects of rumen flora against OTA exposure for dairy cows. Moreover, 100 fresh milk samples randomly collected from different supermarkets in Shanghai were also analyzed, and no positive samples were found, further proving the correctness of the in vivo biotransformation results. Thus, from the currently available data, regarding OTA contamination issues on dairy cows, no significant health risks were related to OTA exposure due to the consumption of these products.

scholarly journals An LC-MS/MS Method for Simultaneous Determination of the Toxic and Active Components of Cortex Periplocae in Rat Plasma and Application to a Pharmacokinetic Study

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Zhen Li ◽  
Yang Li ◽  
Jin Li ◽  
Rui Liu ◽  
Jia Hao ◽  
...  
Keyword(s):  
Oral Administration ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Simple Liquid ◽  
Active Components ◽  
Limit Of Quantification ◽  
Liquid Chromatography Tandem Mass

A sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the toxic and other active components including isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract to rats. Plasma samples were prepared by protein precipitation with methanol. All compounds were separated on a C18 column with gradient elution using acetonitrile and formic acid aqueous solution (0.1%, v/v) as the mobile phase at a flow rate of 0.3 mL/min. The detection of all compounds was accomplished by multiple-reaction monitoring (MRM) in the positive electrospray ionization mode. The LC-MS/MS method exhibited good linearity for five analytes. The lower limit of quantification (LLOQ) was 0.48 ng/mL for scopoletin, periplogenin, and periplocymarin; 2.4 ng/mL for isovanillin and periplocin. The extraction recoveries of all compounds were more than 90% and the RSDs were below 10%. It was found that the absorption of scopoletin and periplocin was rapid in vivo after oral administration of cortex periplocae extract. Furthermore, periplocymarin possessed abundant plasma exposure. The results demonstrated that the validated method was efficiently applied for the pharmacokinetic studies of isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract.

scholarly journals Simultaneous Measurement of Tadehaginoside and its Principal Metabolite in Rats by HPLC–MS/MS and its Application in Pharmacokinetics and Tissue Distribution Study

2021 ◽  
Author(s):  
Cai-Yun Zhang ◽  
Ya-Ting Lu ◽  
Yin-Feng Tan ◽  
Lin Dong ◽  
Zhi-Heng Su ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
High Performance ◽  
Biological Activities ◽  
Intragastric Administration ◽  
Distribution Study ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Tissue Distribution Study

Abstract Background Tadehaginoside, an active ingredient isolated from Tadehagi triquetrum L., exhibited various biological activities. However, the pharmacokinetics and tissue-distribution which affects tadehaginoside’s therapeutic actions and application remain elusive.MethodsTo clarify the metabolism of tadehaginoside in vivo, a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established to detect the level of tadehaginoside in plasma and eleven tat tissues (brain, heart, liver, spleen, lungs, kidneys, stomach, small intestine, skeletal muscle, body fat, and testes). Besides, this validated method was also successfully applied to the quantitative determination of its metabolite, p-hydroxycinnamic acid (HYD) in plasma. The pharmacokinetic and tissue-distribution of tadehaginoside were investigated by this developed method. ResultsThe pharmacokinetic study indicated that tadehaginoside in plasma of rats with intragastric administration showed relatively low concentration may be due to the formation of its metabolite, and the quick absorption of tadehaginoside was detected following intravenous administration. Tissue-distribution study indicated that kidney and spleen were the major distribution organs for tadehaginoside in rats. ConclusionsThese results could provide clues for exploring the bioactivity of tadehaginoside based on its pharmacokinetic characteristics.

scholarly journals Preclinical Pharmacokinetics, Tissue Distribution, and Primary Safety Evaluation of Indo5, a Novel Selective Inhibitor of c-Met and Trks

2021 ◽  
Vol 12 ◽  
Author(s):  
Teng Luo ◽  
Fei-Xiang Zhang ◽  
Ke Zhao ◽  
Hui-Ying Gao ◽  
Shou-Guo Zhang ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Intravenous Injection ◽  
Safety Evaluation ◽  
Rat Plasma ◽  
Selective Inhibitor ◽  
Preclinical Pharmacokinetics ◽  
Normal Number ◽  
Liquid Chromatography Tandem Mass ◽  
Tissue Homogenates

The compound [3-(1H-benzimidazol-2-methylene)-5-(2-methylphenylaminosulfo)-2-indolone], known as Indo5, is a novel selective inhibitor of c-Met and Trks, and it is a promising anticancer candidate against hepatocellular carcinoma (HCC). Assessing the pharmacokinetic properties, tissue distribution, and toxicity of Indo5 is critical for its medicinal evaluation. A series of sensitive and specific liquid chromatography-tandem mass spectrometry methods were developed and validated to determine the concentration of Indo5 in rat plasma and tissue homogenates. These methods were then applied to investigate the pharmacokinetics and tissue distribution of Indo5 in rats. After intravenous injection of Indo5, the maximum concentration (Cmax) and the time at which Cmax was reached (Tmax) were 1,565.3 ± 286.2 ng/ml and 1 min, respectively. After oral administration, Cmax and Tmax were 54.7 ± 10.4 ng/ml and 2.0 ± 0.48 h, respectively. We calculated the absolute oral bioavailability of Indo5 in rats to be 1.59%. Following intravenous injection, the concentrations of Indo5 in various tissues showed the following order: liver > kidney ≈ heart > lung ≈ large intestine ≈ small intestine ≈ stomach > spleen > brain ≈ testes; hence, Indo5 distributed highest in the liver and could not cross the blood–brain or blood–testes barriers. Continuous injection of Indo5 for 21 days did not lead to liver injury, considering unchanged ALT and AST levels, normal histological architecture of the liver, and normal number and frequencies of immune cells in the liver, indicating a very low toxicity of Indo5 in vivo. Collectively, our findings provide a comprehensive understanding of the biological actions of Indo5 in vivo and further support its development as an antitumor treatment for HCC patients.

scholarly journals Human POMC processing in vitro and in vivo revealed by quantitative peptidomics

2018 ◽  
Author(s):  
Peter Kirwan ◽  
Richard Kay ◽  
Bas Brouwers ◽  
Vicente Herranz-Perez ◽  
Magdalena Jura ◽  
...  
Keyword(s):  
Body Weight ◽  
Human Obesity ◽  
Hypothalamic Neurons ◽  
Melanocyte Stimulating Hormone ◽  
Liquid Chromatography Tandem Mass ◽  
Tandem Mass Spectroscopy ◽  
Hypothalamic Tissue ◽  
Human Specific

ABSTRACTHuman obesity can result from the aberrant production or processing of proopiomelanocortin (POMC) in hypothalamic neurons, but it is unclear which human POMC-derived peptides are most relevant to body weight regulation. To address this question, we analysed both hypothalamic neurons derived from human pluripotent stem cells (hPSCs) and primary human hypothalamic tissue using quantitative liquid chromatography tandem mass spectroscopy (LC-MS/MS). In both in vitro- and in vivo-derived samples, we found that POMC was processed into β-melanocyte stimulating hormone (β-MSH), whose existence in the human brain has been controversial. β-MSH and desacetyl α-MSH (d-α-MSH) were produced at roughly equimolar concentrations and in vast excess to acetylated α-MSH (5-to 200-fold), suggesting that the importance of both d-α-MSH and β-MSH to human obesity has been underestimated. Since body weight is sensitive to changes in MSH concentration, we asked whether hPSC-derived hypothalamic neurons could provide mechanistic insights into the processing and secretion of MSH peptides. We found that cultured human hypothalamic neurons appropriately trafficked POMC and its derivatives, and robustly (P<0.0001) secreted them when depolarised. Furthermore, the adipocyte-derived hormone leptin significantly (P<0.01) promoted their production of both d-α-MSH and β-MSH. These results establish hPSC-derived hypothalamic neurons as a model system for studying human-specific aspects of POMC processing that might be therapeutically harnessed to treat obesity.

scholarly journals Determination of myrislignan levels in BALB/c mouse plasma by LC-MS/MS and a comparison of its pharmacokinetics after oral and intraperitoneal administration

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Jili Zhang ◽  
Hongfei Si ◽  
Jichao Sun ◽  
Kun Lv ◽  
Biqing Yan ◽  
...  
Keyword(s):  
Formic Acid ◽  
Intraperitoneal Administration ◽  
Internal Standard ◽  
Pharmacokinetic Parameters ◽  
Clinical Effects ◽  
Limit Of Quantification ◽  
Mouse Plasma ◽  
Relative Standard ◽  
Liquid Chromatography Tandem Mass

Abstract Background Myrislignan is a natural product from Myristica sp. with diverse pharmacological activities. Recently, the anti-Toxoplasma gondii (T. gondii) activity of myrislignan has been proposed, and in vivo studies of its pharmacokinetics in BALB/c mice are necessary to further evaluate the clinical effects of myrislignan. Results In this study, a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantify myrislignan levels in mouse plasma using dehydrodiisoeugenol as an internal standard (IS) in positive ion mode. Chromatographic separation of the analytes was achieved using an ACE Ultracore Super C18 analytical column (2.5 μm, 2.1 × 50 mm) at 30 °C. A gradient mobile phase consisting of water (0.1 % formic acid) and acetonitrile (0.1 % formic acid) was delivered at a flow rate of 0.4 mL/min. Myrislignan and the IS eluted at 1.42 and 1.71 min, respectively. A good excellent linear response across the concentration range of 1-1000 ng/mL was achieved (r2 = 0.9973). The lower limit of quantification (LLOQ) was 1 ng/mL, and the inter- and intra-day accuracy and precision of the method showed relative standard deviations (RSDs) less than 10 %. The method was applied to examine the pharmacokinetics of myrislignan in mouse plasma following a single oral administration of 200 mg/kg or intraperitoneal administration of 50 mg/kg myrislignan, and the bioavailability (F) of orally administered myrislignan was only 1.97 % of the bioavailability of intraperitoneally administered myrislignan. Conclusions A rapid and sensitive LC-MS/MS method has been was developed, validated and successfully used to determine myrislignan levels in mice after oral or intraperitoneal administration. This study is the first to report the pharmacokinetic parameters of myrislignan in mice and to compare its pharmacokinetics after oral and intraperitoneal administration, which will be useful for further research on the administration of myrislignan in animals and humans.

scholarly journals Tissue distribution and tumor concentrations of hydroxychloroquine and quinacrine analogs in mice

2018 ◽  
Author(s):  
Abigail R. Solitro ◽  
Jeffrey P. MacKeigan
Keyword(s):  
Tissue Distribution ◽  
Lupus Erythematosus ◽  
Degradation Process ◽  
The Novel ◽  
Multiple Cancer ◽  
Chromatography Tandem Mass Spectrometry ◽  
Tumor Tissues ◽  
Liquid Chromatography Tandem Mass ◽  
Autophagy Inhibition

ABSTRACTHydroxychloroquine (HCQ) is a 4-aminoquinoline molecule used for the treatment of malaria, and more recently to treat rheumatoid arthritis, systemic lupus erythematosus, and cancer. In cancer, HCQ is being used in multiple cancer clinical trials as an inhibitor of autophagy, a cytosolic degradation process employing the lysosome. Importantly, more potent lysosomotropic agents are being developed as autophagy inhibitors. Additional studies revealed that acridine-based compounds such as quinacrine (QN) increased potency over the 4-aminoquinoline HCQ. In line with these initial discoveries, we performed chemical synthesis of acridine-based compounds and screened for potent autophagy inhibition. The novel compound VATG-027 increased potency and cytotoxicity over HCQ in osteosarcoma and melanoma cell lines, supporting further investigation in vivo. Here, we developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to investigate HCQ, QN, and VATG-027 compound concentrations across various tissue types in mice. This method detected compound concentrations in whole blood, lung, liver, kidney, and subcutaneous tumor tissues. Concentrations of HCQ, QN, and VATG-027 varied within and between tissue types, suggesting unique tissue distribution profiles for 4-aminoquinoline and acridine compounds.

The biochemistry surrounding bovine conceptus elongation†

2019 ◽  
Vol 101 (2) ◽  
pp. 328-337 ◽  
Author(s):  
Constantine A Simintiras ◽  
José M Sánchez ◽  
Michael McDonald ◽  
Patrick Lonergan
Keyword(s):  
Amino Acids ◽  
Linear Rate ◽  
Physiological Conditions ◽  
Uterine Fluid ◽  
Liquid Chromatography Tandem Mass ◽  
Tandem Mass Spectroscopy ◽  
Ultrahigh Performance Liquid Chromatography ◽  
Uterine Secretions

Abstract Conceptus elongation is a fundamental developmental event coinciding with a period of significant pregnancy loss in cattle. The process has yet to be recapitulated in vitro, whereas in vivo it is directly driven by uterine secretions and indirectly influenced by systemic progesterone. To better understand the environment facilitating this critical reproductive phenomenon, we interrogated the biochemical composition of uterine luminal fluid from heifers with high vs physiological circulating progesterone on days 12–14 of the estrous cycle—the window of conceptus elongation-initiation—by high-throughput untargeted ultrahigh-performance liquid chromatography tandem mass spectroscopy. A total of 233 biochemicals were identified, clustering within 8 superpathways [amino acids (33.9%), lipids (32.2%), carbohydrates (8.6%), nucleotides (8.2%), xenobiotics (6.4%), cofactors and vitamins (5.2%), energy substrates (4.7%), and peptides (0.9%)] and spanning 66 metabolic subpathways. Lipids dominated total progesterone (39.1%) and day (57.1%) effects; however, amino acids (48.5%) and nucleotides (14.8%) accounted for most day by progesterone interactions. Corresponding pathways over-represented in response to day and progesterone include (i) methionine, cysteine, s-adenosylmethionine, and taurine (9.3%); (ii) phospholipid (7.4%); and (iii) (hypo)xanthine and inosine purine metabolism (5.6%). Moreover, under physiological conditions, the uterine lumen undergoes a metabolic shift after day 12, and progesterone supplementation increases total uterine luminal biochemical abundance at a linear rate of 0.41-fold day−1–resulting in a difference (P ≤ 0.0001) by day 14. This global metabolic analysis of uterine fluid during the initiation of conceptus elongation offers new insights into the biochemistry of maternal–embryo communication, with implications for improving ruminant fertility.

scholarly journals In Vivo Kinetics and Biotransformation of Aflatoxin B1 in Dairy Cows Based on the Establishment of a Reliable UHPLC-MS/MS Method

2021 ◽  
Vol 9 ◽  
Author(s):  
Wenbo Guo ◽  
Zhichen Fan ◽  
Kai Fan ◽  
Jiajia Meng ◽  
Dongxia Nie ◽  
...  
Keyword(s):  
Dairy Cows ◽  
High Performance ◽  
Life Time ◽  
Limit Of Quantification ◽  
Relative Standard ◽  
Liquid Chromatography Tandem Mass ◽  
Carry Over ◽  
Dose Trial ◽  
Aflatoxin B

The in vivo kinetics of aflatoxin B1 (AFB1) and its carry-over as aflatoxin M1 (AFM1) in milk as well as the toxin loads in the tissue of dairy cows were assessed through a repetitive feeding trial of an AFB1-contaminated diet of 4 μg kg−1 body weight (b.w.) for 13 days. This was followed by a clearance period that ended with a single dose trial of an AFB1-contaminated diet of 40 μg kg−1 b.w. An ultra-high performance liquid chromatography tandem mass spectrometry method was developed and successfully validated by the determination of linearity (R2 ≥ 0.990), sensitivity (lower limit of quantification, 0.1–0.2 ng ml−1), recovery (79.5–111.2%), and precision relative standard deviation (RSD) ≤14.7%) in plasma, milk, and various tissues. The repetitive ingestion of AFB1 indicated that the biotransformation of AFB1 to AFM1 occurred within 48 h, and the clearance period of AFM1 in milk was not more than 2 days. The carry-over rate of AFM1 in milk during the continuous ingestion experiment was in the range of 1.15–2.30% at a steady state. The in vivo kinetic results indicated that AFB1 reached a maximum concentration of 3.8 ± 0.9 ng ml−1 within 35.0 ± 10.2 min and was slowly eliminated from the plasma, with a half-life time (T1/2) of 931.1 ± 30.8 min. Meanwhile, AFM1 reached a plateau in plasma (0.5 ± 0.1 ng ml−1) at 4 h after the ingestion. AFB1 was found in the heart, spleen, lungs, and kidneys at concentrations of 1.6 ± 0.3, 4.1 ± 1.2, 3.3 ± 0.9 and 5.6 ± 1.4 μg kg−1, respectively. AFM1 was observed in the spleen and kidneys at concentrations of only 0.7 ± 0.2 and 0.8 ± 0.1 μg kg−1, respectively. In conclusion, the in vivo kinetics and biotransformation of AFB1 in dairy cows were determined using the developed UHPLC-MS/MS method, and the present findings could be helpful in assessing the health risks to consumers.

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