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#34521133   2021/09/14 To Up

Accumulation of the Major Components from Polygoni Multiflori Radix in Liver and Kidney after Its Long-Term Oral Administrations in Rats.

Although Polygoni Multiflori Radix (PMR) has been widely used as a tonic and an anti-aging remedy for centuries, the extensively reported hepatotoxicity and potential kidney toxicity hindered its safe use in clinical practice. To better understand its toxicokinetics, the current study was proposed, aiming to evaluate the biodistributions of the major PMR components including 2,3,5,4'-tetrahydroxystilbene-2---D-glucopyranoside (TSG), emodin, emodin-8---D-glucopyranoside (EMG) and physcion as well as their corresponding glucuronides following bolus and multiple oral administrations of PMR to rats. Male Sprague-Dawley rats received a bolus dose or 21 days of oral administrations of PMR concentrated granules at 4.12 g/kg (equivalent to 20.6 g/kg raw material). Fifteen minutes after bolus dose or the last dose on day 21, rats were sacrificed and the blood, liver, and kidney were collected for the concentration determination of both parent form and glucuronides of TSG, emodin, EMG, and physcion by HPLC-MS/MS. Among all the tested analytes, TSG, EMG, EMG glucuronides in liver and TSG, EMG, as well as all the glucuronides of these analytes in the kidney demonstrated the most significant accumulation after multiple doses. Moreover, the levels of the parent analytes were all significantly higher in liver and kidney in comparison to their plasma levels. Strong tissue binding of all four analytes and accumulation of TSG, EMG, and EMG glucuronides in the liver and TSG, EMG, as well as the glucuronides of all four analytes in the kidney after multiple dosing of PMR were considered to be associated with its toxicity.
Dan Li, Yuanfeng Lyu, Jiajia Zhao, Xiaoyu Ji, Yufeng Zhang, Zhong Zuo

2686 related Products with: Accumulation of the Major Components from Polygoni Multiflori Radix in Liver and Kidney after Its Long-Term Oral Administrations in Rats.

100 μg 0.1 mg 100 μg50 96 wells100 μg100 μg

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#34521088   2021/09/14 To Up

Characterization of Cycling in a Hoolock Gibbon (Hoolock leuconedys).

Here we examine the patterns of reproductive hormones (progesterone and estrone-3 glucuronide, or E1G) in one female hoolock gibbon (Hoolock leuconedys) housed at the Gibbon Conservation Center, throughout the maturation period. Three hundred forty-five fecal samples were collected from the individual over a 5-year period (2012-2017) beginning at the age of 6 years and ending at the age of 11. The average measured progesterone concentration increased from 19.572 ± 1.706 ng/g feces in 2012 to 107.922 ± 12.094 ng/g feces in 2016/17 (p < 0.00001). The average measured estrogen value increased from 1.234 ± 0.063 ng/g feces in 2012 to 2.783 ± 0.274 ng/g feces in 2016/17 (p < 0.00001). This was accompanied by the emergence of a clear hormonal cycling pattern in the 2016/17 samples that was absent in all earlier samples. These data are consistent with the known sexual maturation period for other gibbon species, which typically occurs between the ages of 6 and 8 but shows some variation. To our knowledge, this is the first hormonal study and first data on cycle length for a hoolock gibbon.
Erin B Guntrum, Alexandra M Haley, Susan W Margulis

1521 related Products with: Characterization of Cycling in a Hoolock Gibbon (Hoolock leuconedys).

100 μg100 μg10 100 μg100 100 μg100 μg1 Set100 μg1-99 mg/ml/ea price x 2

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#34519061   2021/09/13 To Up

Bifunctionalized isotopologues as calibrants for standard-free quantitation of drug metabolites in plasma by liquid chromatography coupled with radiometry and mass spectrometry.

The following method describes a novel workflow that eliminates the need of authentic reference standards for the quantitation of drug metabolites in biological samples using a single multi-isotopically labeled compound bearing both radio and stable isotopes. The resulting radio and stable bifunctionalized isotopologue (RADSTIL) of parent drug is employed as a substrate for in vitro biotransformation to targeted RADSTILs of metabolites as calibrants. Inclusion of a radio label enables both radiometric and mass spectrometric detection. Addition of stable labels ensures subsequent isotopic interference-free quantitation of unlabeled metabolites in preclinical and clinical samples. This affords a more accurate quantitation workflow compared to current semi-quantitation method, which utilizes isotopic interfering radio isotopologues of metabolites alone as calibrants. The proof-of-concept is illustrated with ( C, C )-acetaminophen where in vitro biotransformation produced ( C, C )-sulfate and ( C, C )-glucuronide calibrants. Absolute quantitation of the acetaminophen metabolites was then achieved by liquid chromatography coupled with radiometry and mass spectrometry (LC-RAD/MS). Quantitative data obtained by this method fell within 82-86% of the values from conventional LC-MS/MS method.
Yong Gong, Jie Chen, Heng-Keang Lim, Naidong Weng, Rhys Salter

1333 related Products with: Bifunctionalized isotopologues as calibrants for standard-free quantitation of drug metabolites in plasma by liquid chromatography coupled with radiometry and mass spectrometry.

100 assays100 assays100 assays100 assays100 assays100 assays100 assays100 assays100 assays100 assays100 assays100 assays

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#34515329   2021/09/13 To Up

[Drug use and drug trends in Sweden 2010-2020 - results from urine drug testing in the workplace].

Workplace alcohol and drug testing is increasingly used at employment, for regular checks, and in case of accident, incident, or suspicion of drug exposure. The test results provide valuable objective information about drug use in the society. At the Karolinska University Laboratory (Stockholm, Sweden), the number of samples from drug testing in the workplace has quadrupled in the last decade. Almost all urine samples are tested for amphetamines (amphetamine, methamphetamine and MDMA), benzodiazepines (prescribed substances), cannabis, cocaine and opiates, and some also for alcohol (i.e. the metabolites ethyl glucuronide and ethyl sulfate) and drugs such as tramadol and oxycodone. The proportion of samples that test positive for one or more drugs has increased steadily in recent years to over 5%. Substances commonly detected are, in order of appearance, cannabis, amphetamines (amphetamine and MDMA), benzodiazepines, opiates (mainly codeine and only few due to heroin use), and cocaine. Other common substances are alcohol, tramadol, and oxycodone, but these are only tested for in a limited, and possibly selected, proportion of samples. After an MRO has reviewed the positive laboratory results, about 30% of cases are excluded mainly due to legal prescription as medicine. In 2020, the proportion of positive test results decreased, possibly due to reduced access to illicit drugs during the corona pandemic. In summary, results from drug testing in the workplace indicate that illicit use of drugs shows an increasing trend in Sweden.
Anders Helander, Tomas Villen

2464 related Products with: [Drug use and drug trends in Sweden 2010-2020 - results from urine drug testing in the workplace].

100 assays100 assays100 assays100 assays100 assays100 assays100 assays100 assays100 assays100 assays100 assays100 assays

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#34508925   2021/09/02 To Up

Determination of paracetamol and its metabolites via LC-MS/MS in dried blood volumetric absorptive microsamples: A tool for pharmacokinetic studies.

Paracetamol (acetaminophen, APAP) is the most frequently used analgesic and antipyretic worldwide. Nonetheless, APAP induced hepatotoxicity is the most common cause of acute liver failure in the western world. This hepatotoxicity is related to the metabolism of APAP, via the formation of the electrophilic oxidation product N-acetyl-para-benzoquinone imine. To investigate differences in APAP metabolism in specific patient populations and to optimize dosing regimens, quantification of metabolites from the different metabolic pathways is needed to perform pharmacokinetic (PK) studies. For this purpose, sensitive and short liquid chromatography-tandem mass spectrometry methods were developed for the quantitation of APAP and four of its metabolites (APAP-glucuronide, APAP-sulfate, APAP-mercapturate, and APAP-cysteine) in plasma, whole blood and dried blood microsamples collected via 10 µL volumetric absorptive microsampling (VAMS) devices. The methods were successfully validated based on internationally accepted guidelines (EMA, FDA), encompassing selectivity, evaluation of the calibration model, matrix effect and recovery, accuracy and precision, stability, and dilution integrity. In addition, for the VAMS samples, the effect of the hematocrit on the recovery was evaluated. Successful application on whole blood and plasma, as well as on VAMS samples prepared from venous or capillary blood of patients, demonstrated that the methods were fit-for-purpose and can be used for future PK studies.
Lisa Delahaye, Luc De Baerdemaeker, Christophe P Stove

1497 related Products with: Determination of paracetamol and its metabolites via LC-MS/MS in dried blood volumetric absorptive microsamples: A tool for pharmacokinetic studies.

100Tests1 Set100 μg100 ug/vial1 Set100 μg0.1ml (1mg/ml) 100 UG100 ug/vial400Tests

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#34505743   2021/09/10 To Up

Organ-on-a-chip: Determine feasibility of a human liver microphysiological model to assess long-term steroid metabolites in sports drug testing.

A fundamental challenge in preventive doping research is the study of metabolic pathways of substances banned in sport. However, the pharmacological predictions obtained by conventional in vitro or in vivo animal studies are occasionally of limited transferability to humans according to an inability of in vitro models to mimic higher-order system physiology or due to various species-specific differences using animal models. A more recently established technology for simulating human physiology is the "organ-on-a-chip" principle. In a multi-channel microfluidic cell culture chip, 3-dimensional tissue spheroids, which can constitute artificial and interconnected microscale organs, imitate principles of the human physiology. The objective of this study was to determine if the technology is suitable to adequately predict metabolic profiles of prohibited substances in sport. As model compounds, the frequently misused anabolic steroids, stanozolol and dehydrochloromethyltestosterone (DHCMT) were subjected to human liver spheroids in microfluidic cell culture chips. The metabolite patterns produced and circulating in the chip media were then assessed by LC-HRMS/(MS) at different time-points of up to 14 days of incubation at 37°C. The overall profile of observed glucurono-conjugated stanozolol metabolites excellently matched the commonly found urinary pattern of metabolites, including 3'OH-stanozolol-glucuronde and stanozolol-N-glucuronides. Similarly, but to a lower extent, the DHCMT metabolic profile was in agreement with phase-I and phase-II biotransformation products regularly seen in post-administration urine specimens. In conclusion, this pilot study indicates that the "organ-on-a-chip" technology provides a high degree of conformity with traditional human oral administration studies, providing a promising approach for metabolic profiling in sports drug testing.
Christian Görgens, Anja Patricia Ramme, Sven Guddat, Yvonne Schrader, Annika Winter, Eva-Maria Dehne, Reyk Horland, Mario Thevis

2392 related Products with: Organ-on-a-chip: Determine feasibility of a human liver microphysiological model to assess long-term steroid metabolites in sports drug testing.

100 μg100 μg100 μg100 μg100 100 μg100 μg100 μg100 μg50 100 μg

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#34500483   2021/09/09 To Up

Non-Nutritive Sweeteners in Human Amniotic Fluid and Cord Blood: Evidence of Transplacental Fetal Exposure.

 This study aimed to investigate human fetal exposure to non-nutritive sweeteners (NNS) by analyzing amniotic fluid and umbilical cord blood.
Brianna C Halasa, Allison C Sylvetsky, Ellen M Conway, Eileen L Shouppe, Mary F Walter, Peter J Walter, Hongyi Cai, Lisa Hui, Kristina I Rother

1102 related Products with: Non-Nutritive Sweeteners in Human Amniotic Fluid and Cord Blood: Evidence of Transplacental Fetal Exposure.

1ml1.00 flask 100 UG50ìg100 μg2 100 μg100 μg10 0.1 mg100 μg100 μg

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#34496722   2021/09/15 To Up

Pharmacokinetics and metabolic disposition of a potent and selective kynurenine monooxygenase inhibitor, CHDI-340246, in laboratory animals.

The disposition of a novel kynurenine monooxygenase inhibitor, CHDI-340246, was investigated and in animals., there was minimal metabolic turnover of CHDI-340246 in all species. The protein binding was higher in human plasma (99.7%) relative to other species.In all species, blood clearance was low (<20% of liver blood flow) and volume of distribution was small (<0.5 L/kg). The terminal half-life was longer in monkeys (9 hr) than in mice, rats, or dogs (1-2 hr). CHDI-340246 was orally bioavailable (>60%) in all species.In rats, [C]CHDI-340246 showed wide distribution of radioactivity in all tissues except brain and testes. In rats, the parent drug was the major circulating moiety with minor amounts of a sulphate conjugate of an -dealkylated metabolite. The elimination occurred via the urinary route and to a lesser extent by biliary route, but mostly as metabolites. In cynomolgus monkeys, the parent drug predominated in plasma with only trace amounts of metabolites detected.Acyl glucuronide conjugate of CHDI-340246 was not detected in plasma of rats or monkeys.Overall, the ADME profile of CHDI-340246 was favourable in rats and monkeys for potential evaluation of KMO inhibition in humans.
Vinod Khetarpal, Todd Herbst, Diana Shefchek, Steven Ash, Michael Fitzsimmons, Mark Gohdes, Ignacio Munoz-Sanjuan, Celia Dominguez

1939 related Products with: Pharmacokinetics and metabolic disposition of a potent and selective kynurenine monooxygenase inhibitor, CHDI-340246, in laboratory animals.

96T100 100 assays25 mg 100ul100ug20 1000 tests100 µg100ul20 200ul

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