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Irbesartan (IRB) exerts beneficial effects either alone or in combination with other drugs on numerous diseases, such as cancer, diabetes, and hypertension. However, due to its high lipophilicity, IRB does not possess the optimum pharmacological efficiency. To circumvent this problem, a drug delivery system with 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) was explored. The 1:1 complex between IRB and 2-HP-β-CD was identified through ESI QTF HRMS. Dissolution studies showed a higher dissolution rate of the lyophilized IRB-2-HP-β-CD complex than the tablet containing IRB at pH = 1.2. DSC results revealed the differences of the thermal properties between the complex and various mixtures consisting of the two components, namely IRB and 2-HP-β-CD. Interestingly, depending on the way the mixture preparation was conducted, different association between the two components was observed. Molecular dynamics (MD) simulations predicted the favorable formation of the above complex and identified the dominant interactions between IRB and 2-HP-β-CD. In vitro pharmacological results verified that the inclusion complex not only preserves the binding affinity of IRB for AT1R receptor, but also it slightly increases it. As the complex formulation lacks the problems of the tablet, our approach is a promising new way to improve the efficiency of IRB.

Wastewater-based epidemiology is an additional indicator of drug use that is gaining reliability to complement the current established panel of indicators. The aims of this study were to: (i) assess spatial and temporal trends of population-normalized mass loads of benzoylecgonine, amphetamine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in raw wastewater over 7 years (2011-17); (ii) address overall drug use by estimating the average number of combined doses consumed per day in each city; and (iii) compare these with existing prevalence and seizure data.Analysis of daily raw wastewater composite samples collected over 1 week per year from 2011 to 2017.Catchment areas of 143 wastewater treatment plants in 120 cities in 37 countries.Parent substances (amphetamine, methamphetamine and MDMA) and the metabolites of cocaine (benzoylecgonine) and of ΔBenzoylecgonine was the stimulant metabolite detected at higher loads in southern and western Europe, and amphetamine, MDMA and methamphetamine in East and North-Central Europe. In other continents, methamphetamine showed the highest levels in the United States and Australia and benzoylecgonine in South America. During the reporting period, benzoylecgonine loads increased in general across Europe, amphetamine and methamphetamine levels fluctuated and MDMA underwent an intermittent upsurge.The analysis of wastewater to quantify drug loads provides near real-time drug use estimates that globally correspond to prevalence and seizure data.

This study presents the atmospheric pressure photoionization (APPI) of high-chlorinated (five or more chlorine atoms) polychlorinated biphenyls (PCBs) using toluene as dopant, after liquid chromatographic separation. Mass spectra of PCB 101, 118, 138, 153, 180, 199, 206 and 209 were recorded by using liquid chromatography-APPI-tandem mass spectrometry (LC-APPI-MS/MS) in negative ion full scan mode. Intense peaks appeared at m/z that correspond to (MCl+O) � ions, where M is the analyte molecule. Furthermore, a detailed strategy, which includes designs of experiments, for the development and optimization of LC-APPI-MS/MS methods is described. Following this strategy, a sensitive and accurate method with low instrumental limits of detection, ranging from 0.29pg for PCB 209 to 8.3pg for PCB 101 on column, was developed. For the separation of the analytes, a Waters XSELECT HSS T3 (100mm×2.1mm, 2.5 μm) column was used with methanol/water as elution system. This method was applied for the determination of the above PCBs in water samples (surface water, tap water and treated wastewater). For the extraction of PCBs from water samples, a simple liquid-liquid extraction with dichloromethane was used. Method limits of quantification, ranged from 4.8ngl � 1 , for PCB 199, to 9.4ngl � 1 , for PCB 180, and the recoveries ranged from 73%, for PCB 101, to 96%, for PCB 199. The estimated analytical figures were appropriate for trace analysis of high-chlorinated PCBs in real samples. Copyright © 2014 John Wiley & Sons, Ltd. Additional supporting information may be found in the online version of this article at the publisher's web site.

Molecularly imprinted polymers (MIPs) for bisphenol A (BPA) were prepared by two synthetic routes: semi-covalent and noncovalent methodology. The molecular imprinting effect was evaluated using the polymers in HPLC and SPE. Polymers prepared with noncovalent mode were proven more effective. These polymers were applied in SPE facilitating selective retention of BPA from bottled water and milk. The developed sample preparation was simple and efficient comprising only dilution of milk and MISPE prior to LC-MS analysis. Overall MISPE enhanced sample clean-up. Compared with control nonimprinted polymers and conventional C18 SPE cartridges, the MIPs exhibited selective analyte recognition. The method provided quantitative BPA recoveries, very good reproducibility (% RSDs lower than 7%), and low LOD (0.2 ng/g). MIP interacts similarly with deuterated BPA allowing its use as internal standard in LC-MS. The most critical parameters of MISPE were the organic content in loading-washing medium and the washing volume. Low flow rates in the elution step enhanced extraction recovery. Important advantages of the MIP were: the high breakthrough volumes (> 500 mL of water), high mass capacity (> 10 ng/mg of MIP sorbent), good linearity, and good stability in performance for over 35 cycles of use.

A simple screening method for the determination of toluene-extractable organotin compounds in water samples was developed. Organotins [tributyl tin (TBT), triphenyltin (TPhT) and dibutyl tin (DBT)] were extracted from 2 l of water sample with 10 mL of toluene in the presence of 2.5% (v/v) CH3COOH and 1.2% (w/w) NaCl. Aliquots of 240 µl of the toluene extracts were subjected to electrothermal atomic absorption spectrometry, utilizing the hot injection technique (injection temperature 120 °C) and chemical modification. Under these conditions, an enrichment factor of approximately 2000 was achieved. A comparative study of chemical modifiers was performed. Ten metals and mixtures of them were tested and the best results were obtained with 5 µg of Re. The characteristic mass was 90 pg and the instrumental limit of detection was 0.8 µg l−1 (as Sn), for all compounds tested. The overall limit of detection of the method was 2 ng l−1 (as Sn) for an injection aliquot of 240 µl. Quantitative recoveries were obtained for TBT and TPhT, whereas the DBT recovery was 70%. Addition of 0.5% (w/v) of tropolone in the extraction media resulted in 100% recovery of all organotins tested (TBT, DBT, monobutyl tin and TPhT), whereas, at the same time, inorganic tin was practically not recovered at 100-fold excess. The developed methodology was applied to fresh (lake) and marine waters of Greece and levels between < 2 and 223 ng l−1 were determined. Copyright © 2007 John Wiley & Sons, Ltd.