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This article is protected by copyright. All rights reserved.RATIONALE For pharmaceutical quality control, impurities may have unexpected pharmacological or toxicological effects that seriously impact on safety and efficacy. Arginine vasopressin (AVP) is an important cyclic peptide drug, which is mainly used for the treatment of diabetes insipidus and esophageal varices bleeding. With the improvement of analytical techniques, liquid chromatography-high resolution mass spectrometry (LC/hrMS) has become a critical technique for the challenging task of the. identification and quantification of peptide impurities structurally related to AVP. METHODS An LC/hrMS/MS-based method using a quadruple ion trap-Orbitrap mass spectrometer operated in positive ion ESI mode was developed for the determination and quantification of structurally related peptide impurities in AVP. RESULTS Under optimized experimental conditions, 3 deamidation products, ([Glu4 ]AVP, [Asp5 ]AVP and AVP acid), 2 amino acid deletion impurities (des-Pro7 -AVP and des-Gly9 -AVP), 1 amino acid insertion impurity (endo-Gly10a -AVP), 1 end chain reaction product (N-acetyl-AVP) and 1 AVP isomer were detected. Subsequent quantification using an external standard method allowed the total mass fraction of all structurally related peptide impurities in the AVP study material to be estimated as 30.3 mg/g with an expanded uncertainty of 3.0 mg/g (k=2). CONCLUSION This work complements the AVP impurity profile and facilitates improved separation and discovery of other potential impurities in vasopressin analogues. This article is protected by copyright. All rights reserved.BACKGROUND Compounded preparations (CPs) are an indispensable addition to approved, commercially available drugs (CADs), especially for topical therapy. In Germany, about eight million CPs are prescribed within the statutory health insurance system each year, 50 % thereof by dermatologists. METHODS We analyzed prescribing habits based on a questionnaire sent out to 186 office-based dermatologists and 1,491 pharmacies in the federal states of Rhineland-Palatinate and Saarland. The goal was to improve patient care by collecting and categorizing data in terms of prescription practice and associated challenges in interdisciplinary cooperation. RESULTS Overall, 351 pharmacists (23.5 %) and 53 dermatologists (28.4 %) participated in this survey. The most common reason (83 %) stated for prescribing a CP was the possibility to prescribe large quantities of a given topical medication; CPs were most commonly prescribed for psoriasis and various types of dermatitis. The most frequently prescribed active pharmaceutical ingredients were triamcinolone (80 %), erythromycin (78.3 %) and clotrimazole (72.5 %). Fifty-eight percent of pharmacists reported that the collaboration with dermatologists was "associated with problems"; 34 % complained about insufficient communication. CONCLUSIONS CPs are essential for optimizing patient care. Interdisciplinary cooperation poses a challenge to both physicians and pharmacists. In this context, it is important to increase collaborative efforts in terms of training and continuing medical education. Further studies on CPs are required to better elucidate the challenges and opportunities associated with their prescription. © 2020 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.Spondias mobin leaves have been traditionally used for treating cold sores. The study investigated the mechanism of antiherpes action of S. mombin extract, fractions, and geraniin. Different concentrations of samples were used to evaluate the in vitro antiherpes activity (anti-HSV-1) in virucidal, post-infection, attachment, and penetration assays. The mechanism of action of geraniin was investigated considering the glycoproteins gB and gD of HSV-1 surface as potential molecular targets. selleck kinase inhibitor Molecular docking simulations were carried out for both in order to determine the possible binding mode position of geraniin at the activity sites. The binding mode position was posteriorly optimized considering the flexibility of the glycoproteins. The chemical analysis of samples was performed by LC-MS and revealed the presence of 22 substances, which are hydrolysable tannins, O-glycosylated flavonoids, phenolic acids, and a carbohydrate. The extract, tannin-rich fraction and geraniin showed important in vitro virucidal activity through blocking viral attachment but showed no relevant inhibition of viral penetration. The in silico approaches demonstrated a high number of potential strong intermolecular interactions as hydrogen bonds between geraniin and the activity site of the glycoproteins, particularly the glycoprotein gB. In silico experiments indicated that geraniin is at least partially responsible for the anti-herpes activity through interaction with the viral surface glycoprotein gB, which is responsible for viral adsorption. These results highlight the therapeutic potential of S. mombin anti-herpes treatment and provides support for its traditional purposes. However, further studies are required to validate the antiviral activities in vivo, as well as efficacy in humans. Georg Thieme Verlag KG Stuttgart · New York.We develop a Bayesian nonparametric (BNP) approach to evaluate the causal effect of treatment in a randomized trial where a nonterminal event may be censored by a terminal event, but not vice versa (i.e., semi-competing risks). Based on the idea of principal stratification, we define a novel estimand for the causal effect of treatment on the nonterminal event. We introduce identification assumptions, indexed by a sensitivity parameter, and show how to draw inference using our BNP approach. We conduct simulation studies and illustrate our methodology using data from a brain cancer trial. The R code implementing our model and algorithm is available for download at https//github.com/YanxunXu/BaySemiCompeting. © The Author 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND Despite treatment with pancreatic enzyme replacement therapy (PERT), patients with cystic fibrosis (CF) can still suffer from fat malabsorption. A cause could be low intestinal pH disabling PERT. The aim of this study was to assess the association between faecal pH (as intestinal pH surrogate) and coefficient of fat absorption (CFA). Additionally, faecal free fatty acids (FFAs) were quantified to determine the amount of digested, but unabsorbed fat. METHODS In a 24-h pilot study, CF patients followed a standardised diet with fixed PERT doses, corresponding to theoretical optimal doses determined by an in vitro digestion model. Study variables were faecal pH, fat and FFA excretion, CFA and transit time. Linear mixed regression models were applied to explore associations. RESULTS In 43 patients, median (1st, 3rd quartile) faecal pH and CFA were 6.1% (5.8, 6.4) and 90% (84, 94), and they were positively associated (p  less then  0.001). An inverse relationship was found between faecal pH and total fat excretion (p  less then  0.