Detection and identification of imperatorin metabolites in rat, dog, monkey, and human liver microsomes by ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry and Compound Discoverer software.

Imperatorin, a furanocoumarin that widely exists in many umbelliferous herbs, has been demonstrated to have a variety of pharmacological effects, including anti-inflammatory, antiosteoporosis, and antitumor activities. The purpose of this study was to investigate the metabolism of imperatorin using liver microsomes. The metabolites were generated by individually incubating imperatorin with rat, dog, monkey, and human liver microsomes. To trap the reactive metabolites during microsomal metabolism, glutathione (GSH) was included in the incubation. A LC technique coupled with benchtop orbitrap MS with full mass/data-dependent tandem mass spectrometry acquisition mode was used to detect and identify the generated metabolites. The possible structures of the metabolites were characterized according to their accurate masses and fragment ions. Under the current conditions, a total of 10 metabolites, including four GSH adducts, were identified. The results indicated that imperatorin underwent extensive metabolic reactions including hydroxylation, oxidation, glucuronidation, and GSH conjugation. This study provides essential data on the metabolism of imperatorin, which will be helpful for us to understand the safety and efficacy of this bioactive compound.

Establishment and evaluation of a novel practical tool for the diagnosis of pre-sarcopenia in young people with diabetes mellitus.

OBJECTIVE: Sarcopenia has been recognized as a third category of complications in people with diabetes. However, few studies focus on the reduction of skeletal muscle mass in young people with diabetes. The aim of this study was to investigate risk factors of pre-sarcopenia in young patients with diabetes and establish a practical tool to diagnose pre-sarcopenia in those people. METHODS: Patients (n = 1246) enrolled from the National Health and Nutrition Examination Survey (NHANES) cycle year of 2011 to 2018 were randomly divided into the training set and validation set. The all-subsets regression analysis was used to select the risk factors of pre-sarcopenia. A nomogram model for the prediction of pre-sarcopenia in the diabetic population was established based on the risk factors. The model was evaluated by the area under the receiver operating characteristic curve for discrimination, calibration curves for calibration, and decision curve analysis curves for clinical utility. RESULTS: In this study, gender, height, and waist circumference were elected as predictive factors for pre-sarcopenia. The nomogram model presented excellent discrimination in training and validation sets with areas under the curve of 0.907 and 0.912, respectively. The calibration curve illustrated excellent calibration, and the decision curve analysis showed a wide range of good clinical utility. CONCLUSIONS: This study develops a novel nomogram that integrates gender, height, and waist circumference and can be used to easily predict pre-sarcopenia in diabetics. The novel screen tool is accurate, specific, and low-cost, highlighting its potential value in clinical application.

Development and validation of a simple and sensitive high-resolution LC/MS method for determination of PF-04620110 in dog plasma: Application to a pharmacokinetic study.

In this study, a more sensitive and reliable quantitative method based on ultra-high performance liquid chromatography coupled with Q-Exactive-Orbitrap-MS in full-mass scan was developed and validated for the determination of PF-04620110 in dog plasma. After protein precipitation with acetonitrile, the sample separations were carried out on an Acquity BEH C18 column with 1 mm ammonium acetate in water and acetonitrile containing 0.1% acetic acid as mobile phase, at a flow rate of 0.4 mL/min. The assay showed excellent linearity over the concentration range of 1-2000 ng/mL with correlation coefficient >0.9980 (r > 0.9980). The LLOQ was 1 ng/mL. The inter- and intra-day precision (RSD, %) was within 9.69% while the accuracy (RE, %) was in the range of -8.59-11.24%. The extraction recovery was >85.37% and the assay was free of matrix effects. PF-04620110 was demonstrated to be stable under various processing and handing conditions. The validated method was successfully applied to the pharmacokinetic study of PF-04620110 in dogs and the results revealed that PF-04620110 was slowly eliminated from plasma with a clearance of 60.81 ± 7.11 mL/h/kg for intravenous administration and 81.44 ± 25.79 mL/h/kg for oral administration. The oral bioavailability was determined to be 77.89% in dogs.