盐酸雷尼替丁与7,7,8,8-四氰基对二次甲基苯醌荷移反应的研究

以盐酸雷尼替丁为电子给体,7,7,8,8-四氰基对二次甲基苯醌(TCNQ)为电子受体,研究了它们之间形成电荷转移络合物的最佳条件.结果表明:在丙酮介质中,二者于50℃下60min即可形成1:1络合物,室温下至少稳定4h.荷移络合物的最大吸收波长为845nm,表观摩尔吸光系数为1.70×104L·mol-1·cm-1,在1-20mg·L-1范围内符合比耳定律.基于以上反应建立本方法,用于测定制剂中盐酸雷尼替丁的含量,结果与药典方法一致,回收率为99.27%-101.40%,相对标准偏差为1.56%(n=10).     

盐酸半胱氨酸和四氯对苯醌的荷移反应

研究了盐酸半胱氨酸与四氯对苯醌的荷移反应,确定了荷移反应的最佳条件.结果表明,在硼砂介质中,两者可形成1:1的稳定络合物,其λmax=354nm,表观摩尔吸光系数ε=8.7×103L·mol-1·cm-1,在2-18μg/mL的范围内符合比耳定律.本方法测定药物制剂含量与文献方法一致,回收率在99.83%-102.4%,相对标准偏差在1.9%以内.     

New Electrochemical Sensor of Prolonged Application for Metformin Determination Based on Hydrated Ruthenium Dioxide‐Carbon Black‐Nafion Modified Glassy Carbon Electrode

Metformin (MET) is an antidiabetic drug most commonly used in treatment of diabetes mellitus type 2 (T2D). Adsorptive stripping voltammetric method using carbon black – hydrated ruthenium dioxide – Nafion modified glassy carbon electrode (CB‐RuO₂‐Nafion GC electrode) have been developed for metformin determination in pharmaceutical formulations. By using ruthenium dioxide, electrode's lifespan was extended to at least 3 weeks (change of metrological parameters estimated as 3–4 %) what is an excellent result concerning other solutions previously described in the literature. Moreover the fabrication of the sensor is simple and fast. Deposition step was carried out at the potential 0 mV for 15 s. The best results were obtained in 0.05 M acetate buffer (pH 4.6). Important aspect was fixed MET : Cu(II) ratio equal to 1 : 8, otherwise linear dependence between register current and MET concentration could not be obtained. In addition, a significant improvement in the parameters of the calibration curve was obtained. Limit of detection was equal to 0.7 μM. Developed method was successfully applied in analysis of 2 pharmaceuticals products and in wastewater and river water. Accuracy of the method was estimated using recoveries, which were in the range 101–110 %. In order to adapt developed system into hydrodynamic conditions, amperometry in hydrodynamic transport conditions and flow injection analysis (FIA) measurements have been conducted. Conducted FIA measurements prove that developed method has potential for application in automized flow systems without frequent calibration.     

Dy(III) complexes of metformin Schiff-bases as glucose probe: synthesis,spectral, and thermal properties

Complexes of Dy³⁺ with metformin-Schiff-bases of salicylaldehyde (HL¹); 2,3-dihydroxybenzaldehyde (H₂L²); 2,4-dihydroxybenzaldehyde (H₂L³); 2,5-dihydroxybenzaldehyde (H₂L⁴); 3,4-dihydroxybenzaldehyde (H₂L⁵); and 2-hydroxynaphthaldehyde (HL⁶) were synthesized by template reactions. The new compounds were characterized through elemental analysis, conductivity and magnetic moment measurements, IR, UV–vis, fluorescence, GC–MS, and XRD spectroscopies. The complexes are seven coordinate with formulas [DyL^1–4,6(NO₃)₂(H₂O)₂]·nH₂O where n?=?2, 2½, 4, 2, 2 and [DyL⁵(NO₃)(H₂O)₄]·2H₂O. TGA, DTG, and DTA analyses confirmed the suggested stereochemistry and subsequently the proposed mechanism of thermal decomposition. Kinetic and thermodynamic parameters were calculated for the second decomposition step. Thus, we report the ability of using the prepared complexes in the detection of glucose at physiological conditions using UV–vis and fluorescence spectroscopy as well as viscosity measurements, where the association constants were calculated.

     

荧光分光光度法直接测定盐酸异丙嗪片剂及注射液的含量

以０．０００１ｍｏｌ／Ｌ盐酸的溶剂,３０３ｎｍ为激发波和ｎｍ为发射波和散荧光分光光度法直接测定盐酸异丙嗪片剂及注射液中盐酸异丙嗪的含量。盐酸异丙嗪在０．１～１０．０μｇ／ｍＬ浓度范围呈良好线性。片剂及注射液的测定平均变异系数分别为０．３１％和０．４５％,回收率分别为９９．９％和９９．６％。     

Effectively designed molecularly imprinted polymers for selective isolation of the antidiabetic drug metformin and its transformation product guanylurea from aqueous media

In the present study, two novel molecularly imprinted polymers (MIPs) with remarkable recognition properties for metformin and its transformation product, guanylurea, have been prepared for their selective, enrichment, isolation and removal from aqueous media. The prepared adsorbents were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and swelling experiments. The performance of the prepared MIPs was evaluated by various parameters including the influence of pH, contact time, temperature and initial compound concentration. The effects on the adsorption behavior of the removal process parameters were studied and the equilibrium data were fitted by the Langmuir and Freundlich models. Due to the imprinting effect, adsorption performance of MIPs was always superior to its corresponding NIP (non-imprinted polymer), with maximum adsorption capacity ∼80 mg g⁻¹ for both MIPs. Stability and reusability of the MIPs up to the 5th cycle meant that they could be applied repeatedly without losing substantial removal ability. In the next step, the prepared MIP nanoparticles were evaluated as sorbents in a dispersive solid phase extraction (D-SPE) configuration for selective enrichment and determination of metformin and guanylurea in different aqueous matrices. Under the working extraction conditions, the D-SPE method showed good linearity in the range of 50–1000 ng L⁻¹, repeatability of the extractions (RSD 2.1–5.1%, n = 3), and low limits of detection (1.5–3.4 ng L⁻¹). The expanded uncertainty of the data obtained was estimated following a bottom-up approach. The proposed method combined the advantages of MIPs and D-SPE, and it could become an alternative tool for analyzing the residues of METF and its transformation product GUA in complex water matrices, such as wastewaters.     

钯(II)-盐酸二甲双胍-曙红Y缔合体系的共振瑞利散射、二级散射和倍频散射光谱及分析应用

在pH3.5的HAc-NaAc缓冲介质中,盐酸二甲双胍(MFH)与Pd(Ⅱ)形成阳离子螯合物,它能进一步与酸性染料曙红Y(EY)的阴离子反应,形成离子缔合物。三元离子缔合物的生成将引起共振瑞利散射(RRS)、二级散射(SOS)和倍频散射(FDS)光谱显著增强,其最大散射波长分别位于292、540和327 nm。在一定范围内,三种散射信号的增强(ΔI_(RRS),ΔI_(SOS)和ΔI_(FDS))均与MFH的浓度呈线性关系。方法具有较高的灵敏度,RRS、SOS和FDS法对MFH的检出限(3σ)分别为1.7、13.2和22.7 ng·m L-1。考察了适宜的反应条件和共存物质的影响,结果表明该方法选择性良好。探讨了缔合物生成及散射增强的机理。据此,提出了简便、快速、准确且高灵敏度的测定痕量MFH的光散射新方法,并应用于片剂和尿样中MFH的测定,结果满意。     

Synthesis of 1-aryl indoles via coupling reaction of indoles and aryl halides catalyzed by CuI/metformin

Ullmann-type C–N coupling reaction has been developed for the synthesis of 1-aryl indole derivatives by indoles and aryl halides in the presence of CuI/metformin (CuI/Met) in DMF. This method is very easy, rapid, and high yielding reaction for the synthesis of 1-aryl indoles. In particular, the metformin, which is used as ligand, is inexpensive and nontoxic that is considered to be relatively environmentally benign.     

Analytical quality by design in the development of a cyclodextrin‐modified capillary electrophoresis method for the assay of metformin and its related substances

Quality by Design (QbD) is a new paradigm of quality to be applied to pharmaceutical products and processes, recently encouraged by International Conference on Harmonisation guidelines. In this paper QbD approach was applied to the development of a CE method for the simultaneous assay of metformin hydrochloride (MET) and its main impurities. QbD strategy was focused on electrophoretic process understanding, and the analytical method was thoroughly evaluated by applying risk assessment and chemometric tools. Method scouting allowed CD‐CZE based on the addition of carboxymethyl‐β‐CD to Britton‐Robinson acidic buffer to be chosen as operative mode. Seven critical process parameters (CPPs) were selected, related to capillary, injection, BGE and instrumental settings. The effect of the different levels of the CPPs on critical quality attributes (CQAs), e.g. critical resolution values and analysis time, was evaluated in a screening study. Response surface methodology led to draw contour plots and sweet spot plots. The definition of design space was accomplished by applying Monte‐Carlo simulations, thus identifying by risk of failure maps a multivariate zone where the CQAs fulfilled the requirements with a selected probability. Finally, a control strategy was designed and the method was applied to a real sample of MET tablets.     

Ready Biodegradability study and insights with ultra-high-performance liquid chromatograph coupled to a quadrupole time of flight of a Metformin-based drug and of Metarecod,a natural substance-based medical device

Drugs are indispensable products with incontrovertible benefits to human health and lifestyle. However, due to their overuse and improper disposal, unwanted residues of active pharmaceutical ingredients (APIs) have been found in different compartments of the environment and now are considered as contaminants of emerging concern (CECs). Therefore, they are very likely to have a boomerang effect on human health, because they can enter into the food cycle. In the current legislation framework, one of the tests first used to evaluate biodegradation of APIs as well as chemical compounds is the ready biodegradability test (RBT). This test can be performed according to a series of protocols prepared by Organization for Economic Co-operation and Development (OECD) and usually is carried out on pure compounds. RBTs, largely used due to their relatively low cost, perceived standardization, and straightforward implementation and interpretation, are known to have a number of well-documented limitations. In this work, following a recently reported approach, we propose to improve the evaluation of the RBT results applying advanced analytical techniques based on mass spectrometry, not only to the APIs but also to complex formulated products, as the biodegradability can potentially be affected by the formulation. We evaluated the ready biodegradability of two therapeutic products, Product A —a drug based on Metformin—and Product B —Metarecod a natural substance-based medical device—through the acquisition of the fingerprint by ultra-high-performance chromatograph coupled to a quadrupole time of flight (UHPLC-qToF) of samples coming from the RBT OECD 301F. Untargeted and targeted evaluation confirmed the different behavior of the two products during the respirometry-manometric test, which showed a difficulty of the Metformin-based drug to come back in the life cycle, whereas Metarecod resulted ready biodegradable. The positive results of this research will hopefully be useful in the future for a better evaluation of the risk/benefit ratio of APIs extended to the environment.