Evaluation of pharmaceutical activities of G-protein coupled receptor targeted pharmaceuticals in Chinese wastewater effluent

The occurrence of biologically active pharmaceuticals in aquatic environments raised the potential risks to aquatic species. Among these marketed biological active pharmaceuticals, it has been estimated that 40% of them target G-protein-coupled receptors (GPCRs). We have illustrated pharmaceutical activities of GPCR targeted pharmaceuticals in English and Japanese wastewater by the in vitro transforming growth factor-α (TGFα) shedding assay. However, as the most important producer and consumer of pharmaceuticals, the occurrence of GPCR targeted pharmaceuticals in China had remained unclear. In this study, we investigated the pharmaceutical activities of GPCR targeted pharmaceuticals in secondary effluents of Chinese wastewater treatment plants. We discovered antagonistic activities against angiotensin (AT1) receptor at up to 7.2 × 102 ng-valsartan-equivalent quantity/L in Chinese wastewater for the first time as well as agonistic activities against dopamine (D2) receptor. Furthermore, in parallel with the assay, we determined concentrations of GPCR targeted pharmaceuticals in target wastewater by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). Through the comparison of predicted antagonistic activities calculated by concentrations and potency values from the assay, we found that the measured antagonistic activities against AT1 receptor from the assay were higher than the predicted AT1 activities from valsartan, irbesartan, and losartan, indicating the potential existence of other unknown AT1 antagonists in wastewater.     

Determination of nonsteroidal antiinflammatory drugs in water samples using liquid chromatography coupled with diode-array detector and mass spectrometry

An analytical method for the determination of trace levels of six different nonsteroidal antiinflammatory drugs (NSAIDs) in water samples has been developed and validated. Environmentally relevant pharmaceuticals were chosen according to human consumption in Poland. Final analysis of the target compounds was performed by RP LC-diode-array detection-MS, whereas sample preparation included an SPE step. For this SPE step, a number of packing materials, such as LiChrolut RP-18, calixarene, Strata-X, BAKERBOND Narc-2, BAKERBOND Polar Plus, BAKERBOND styrene divinylbenzene-1, and Discovery DSC-18, were used, and their respective advantages and disadvantages in this study were discussed. The RP-18 phase was found to be the most retentive for all analytes. The detection limits for compounds in surface waters were varied from 0.005 for diflunisal to 0.095 microg/L for ibuprofen. The average recoveries of NSAIDs from the surface water samples ranged from 80 up to 103%. RSD value is relatively low (from 4% for fenoprofen up to 8% for ibuprofen). The performance of the method was tested with several environmental water samples.     

Application of PLS regression to fluorimetric data for the determination of furosemide and triamterene in pharmaceutical preparations and triamterene in urine

Multivariate calibration methods that use fluorescence data for the simultaneous determination of furosemide and triamterene were developed. One of the most salient advantages of them is that the vast amount of information provided by the whole spectrum of the sample is not required. This makes analyses simple and fast. The methods require selecting chemometric parameters such as the specific spectral region and number of factors to be used. Both spectral region and number of factors are selected, simultaneously, by minimising the prediction residual error sum of squares (PRESS).The proposed methods were used for the simultaneous determination of the two drugs in real samples (pharmaceutical preparations) with no excipient separation pre-treatment, with furosemide and triamterene contents of 1.68E−3 to 4.31E−2 and 1.03E−3 to 3.12E−2 μg ml⁻¹, respectively; as well as that of triamterene at concentrations of 5.00E−4 to 5.80E−3 μg ml⁻¹ in urine samples. The ability to construct the calibration validation sets directly from the urine samples itself avoids the need to consider matrix interferences or to pre-treat the sample and/or separate some analytes The results were quite good in all cases.     

Development of a novel analytical method for determination of chondroitin sulfate using an in-capillary enzyme reaction

A novel analytical method for determination of total amount of chondroitin sulfate (CS) based on its conversion to desulfated chondro-disaccharide via an enzyme-catalyzed reaction, was developed. Using the in-capillary enzyme reaction, the method was also applied to the successful construction of an on-line analytical system. Within this system, electrophoretic migration was used to mix zones containing the enzyme mixture (chondroitinase ABC, chondro-4-sulfatase, chondro-6-sulfatase and 2-o-sulfatase) and the substrate (CS). The reaction was then allowed to proceed in the presence of a weak electric field and, finally, the product (desulfated chondro-disaccharide) of enzyme reaction migrated to the detector under the influence of an applied electric field. A polyvinyl alcohol-coated capillary was used to reduce protein adsorption. Desulfated chondro-disaccharide was successfully migrated toward the anode in 10 mM Tris-acetate buffer (pH 7.0) under reversed polarity and detected at 232 nm. The established method was validated and demonstrated to be applicable in the determination of total amount of CS in a commercial ophthalmic solution. No interference from the formulation excipients was observed. Good linearity was obtained, with correlation coefficients above 0.999. Recoveries and precisions ranged from 100.0 to 100.5%, and from 0.2 to 0.6% of the relative standard deviation, respectively. Good agreement was obtained between the established method and traditional photometric method based on carbazole reaction. In this study, application of the method to disaccharide compositional analysis was also performed.     

Steam distillation-solid-phase microextraction for the detection of Ephedra sinica in herbal preparations

A new method involving concurrent solid-phase microextraction combined with continuous hydrodistillation of essential oil was developed. This new methodology allowed for the detection by GC-MS of very small amounts of a diagnostic peak for the authentication of Ephedra sinica, in a short period of time and using only small sample sizes. This diagnostic peak was identified as 4-vinylanisole, and elucidated from the chromatographic profile allowed for the identification of a sample as E. sinica among other species investigated in this study. To the best of our knowledge this is the first report on using continuous solid-phase microextraction coupled to hydrodistillation for the investigation of essential oil components, and the first report of 4-vinylanisole as a marker compound for E. sinica. A total of 46 collections representing 21 species of Ephedra were studied.     

圆二色光谱及其在药物研究方面的应用

对圆二色光谱技术在手性化合物分析中的应用进展进行综述,简单介绍了圆二色光谱的原理和特点,着重阐述了圆二色光谱在药物研究领域中的应用,初步探讨了HPLC-CD联用在该领域的应用.     

Quantitative and selective analysis of lactose by capillary electrophoresis

Summary A CE method has been validated for the analysis of batches of lactose used as a pharmaceutical raw material. This method was shown to be selective for lactose and was found to be quantitative. The separation was achieved due to on-capillary chelation of the lactose with borate ion. The resulting complex was detected at 195nm. An internal standard is employed to improve injection precision and detector linearity. A system peak occurred in the separation and was systematically investigated to show that it was not sample related. The method was validated and successfully submitted to regulatory authorities and is now in routine use in a number of our quality control laboratories.     

Requirements and tests for HPLC apparatus and methods in pharmaceutical quality control

Summary One possible method has been demonstrated for pharmaceutical quality control which is not restricted to this field and fulfils and documents the prerequisites for reliable, accurate and precise HPLC analysis. This includes validation which shows that the method is able in principle to fulfil the requirements, the apparatus test which shows that the apparatus generally works correctly and precisely and the system suitability test which shows that the method provides accurate and precise results on this apparatus and with this column for the analysis in question when other non-equipment and non-method-induced errors are excluded.     

A review on pharmaceuticals removal from waters by single and combined biological,membrane filtration and ultrasound systems

Contaminants of emerging concern (CEC) such as pharmaceuticals commonly found in urban and industrial wastewater are a potential threat to human health and have negative environmental impact. Most wastewater treatment plants cannot efficiently remove these compounds and therefore, many pharmaceuticals end up in aquatic ecosystems, inducing problems such as toxicity and antibiotic-resistance. This review reports the extent of pharmaceutical removal by individual processes such as bioreactors, advanced oxidation processes and membrane filtration systems, all of which are not 100% efficient and can lead to the direct discharge of pharmaceuticals into water bodies. Also, the importance of understanding biotransformation of pharmaceutical compounds during biological and ultrasound treatment, and its impact on treatment efficacy will be reviewed. Different combinations of the processes above, either as an integrated configuration or in series, will be discussed in terms of their degradation efficiency and scale-up capabilities. The trace quantities of pharmaceutical compounds in wastewater and scale-up issues of ultrasound highlight the importance of membrane filtration as a concentration and volume reduction treatment step for wastewater, which could subsequently be treated by ultrasound.     

Novel Potentiometric Sensors for Determination of Melatonin and Oxomemazine in Biological Samples and in Pharmaceutical Formulations

Simple, selective and accurate sensors were developed for the determination of melatonin and oxomemazine in biological samples (urine) and in pharmaceutical preparations. Potentiometric measurements were based on bismus tetraiodate‐drug ion‐pair as novel electroactive materials incorporating a plasticized PVC membrane with o‐nitrophenyl octyl ether or dioctyl phthalate. Each sensor was conditioned for at least two days in 0.1 M drug solution before use. It exhibited fast and stable Nernstian response for melatonin and oxomemazine over the concentration range of 1.0×10^?6–1.0×10^?2 M and 1.0×10^?5–1.0×10^?2 M, pH range of 3.0–6.5 and 3.5–6.0 for melatonin and oxomemazine sensors, respectively. Results with an average recovery not more than 101 % and a mean standard deviation less than 1.0 % of the nominal were obtained for the four sensors. The sensors showed reasonable selectivity towards investigated drugs in presence of many cations.