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.

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 A simple liquid chromatography-tandem mass spectrometry method to accurately determine the novel third-generation EGFR-TKI naquotinib with its applicability to metabolic stability assessment

RSC Advances ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 4862-4869 ◽  
Author(s):  
Haitham Alrabiah ◽  
Adnan A. Kadi ◽  
Mohamed W. Attwa ◽  
Ali S. Abdelhameed
Keyword(s):  
Mass Spectrometry ◽  
Simple Liquid ◽  
Tandem Mass ◽  
Third Generation ◽  
The Novel ◽  
Stability Assessment ◽  
Spectrometry Method ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Egfr Tki

The first established LC-MS/MS method for NQT analysis. NQT was shown to be moderately excreted from the human body.

scholarly journals Development and Validation of a Bioanalytical Method for 3′- and 6′-Sialyllactose in Minipig Liver and Kidney Using Liquid Chromatography-Tandem Mass Spectrometry and Its Application to Analysis of Tissue Distribution

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5721
Author(s):  
Han Young Eom ◽  
Seok-In Jang ◽  
Jong-Hwa Lee
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Tissue Distribution ◽  
Gradient Elution ◽  
Tandem Mass ◽  
Bioanalytical Method ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Liver And Kidney

Breast milk contains human milk oligosaccharides (HMOs), including sialyllactose (SL). SL is composed of sialic acid and lactose, and is divided into 3′-SL and 6′-SL according to the binding position. SL has immunoprotective effects against bacteria and viruses, and acts as a probiotic in the gastrointestinal tract. In this study, we developed a bioanalytical method for simultaneous analysis of 3′-SL and 6′-SL in liver and kidney tissues of Yucatan minipigs using liquid chromatography–tandem mass spectrometry (LC-MS/MS) under conditions optimized in our previous study. LC-MS/MS was performed using a hydrophilic interaction liquid chromatography (HILIC) column (50 mm × 2.1 mm, 3 μm) with a mobile phase consisting of 10 mM ammonium acetate in water (pH 4.5) and acetonitrile with gradient elution at a flow rate of 0.3 mL/min. A surrogate matrix method using water was applied for analysis of endogenous SL. The developed method was validated with regard to selectivity, linearity, precision, accuracy, the matrix effect, recovery, parallelism, dilution integrity, carryover, and stability according to the US Food and Drug Administration guidelines. We performed a tissue distribution study of minipigs, and analyzed liver and kidney tissues using the developed method to determine the tissue distribution of 3′-SL and 6′-SL. The tissue concentrations of 3′-SL and 6′-SL were readily measurable, suggesting that the method would be useful for evaluating the tissue distributions of these compounds in minipigs.

scholarly journals Bile Acids Quantification by Liquid Chromatography–Tandem Mass Spectrometry: Method Validation, Reference Range, and Interference Study

Diagnostics ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 462 ◽  
Author(s):  
Elisa Danese ◽  
Davide Negrini ◽  
Mairi Pucci ◽  
Simone De Nitto ◽  
Davide Ambrogi ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Healthy Subjects ◽  
Reference Range ◽  
Tandem Mass ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Interference Study

Bile acids (BA) play a pivotal role in cholesterol metabolism. Their blood concentration has also been proposed as new prognostic and diagnostic indicator of hepatobiliary, intestinal, and cardiovascular disease. Liquid chromatography tandem mass spectrometry (LC–MS/MS) currently represents the gold standard for analysis of BA profile in biological samples. We report here development and validation of a LC–MS/MS technique for simultaneously quantifying 15 BA species in serum samples. We also established a reference range for adult healthy subjects (n = 130) and performed a preliminary evaluation of in vitro and in vivo interference. The method displayed good linearity, with high regression coefficients (>0.99) over a range of 5 ng/mL (lower limit of quantification, LLOQ) and 5000 ng/mL for all analytes tested. The accuracies were between 85–115%. Both intra- and inter-assay imprecision was <10%. The recoveries ranged between 92–110%. Each of the tested BA species (assessed on three concentrations) were stable for 15 days at room temperature, 4 °C, and −20 °C. The in vitro study did not reveal any interference from triglycerides, bilirubin, or cell-free hemoglobin. The in vivo interference study showed that pools obtained from hyper-cholesterolemic patients and hyper-bilirubinemic patients due to post-hepatic jaundice for benign cholestasis, cholangiocarcinoma and pancreatic head tumors had clearly distinct patterns of BA concentrations compared with a pool obtained from samples of healthy subjects. In conclusion, this study proposes a new suitable candidate method for identification and quantitation of BA in biological samples and provides new insight into a number of variables that should be taken into account when investigating pathophysiological changes of BA in human diseases.

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