Simultaneous determination of rosiglitazone and metformin in plasma by gradient liquid chromatography with UV detection

A novel, fast and simple liquid chromatographic method was developed and validated for the simultaneous determination of rosiglitazone and metformin in human plasma. The analysis was performed on a phenyl column (250 mm × 4.6 mm i.d., 5 μm) using a gradient method starting with mobile phase composed of acetonitrile:5 mM acetate buffer pH 5.5 (75:25, v/v). The flow rate was 1 mL min⁻¹. UV detection was performed at 245 nm and verapamil was used as internal standard. The total run time was less than 10 min. Sample preparation included a simple protein precipitation step with acetonitrile. Validation experiments were performed to demonstrate stability, specificity, sensitivity, linearity, accuracy, precision and robustness. The limit of quantification was 100 ng mL⁻¹ for rosiglitazone and 250 ng mL⁻¹ for metformin. The extraction recoveries were 100.02-105.0% for rosiglitazone and 105.64-103.88% for metformin. The method was applied with success to plasma samples obtained from diabetic patients undergoing treatment with rosiglitazone and metformin.     

GGA-based analysis of the metformin adsorption on BN nanotubes

Density functional theory (DFT) studies are done to investigate structural and electronic properties of (5,5) chirality single walls boron nitride nanotubes (BNNTs) in the armchair model interacting with metformin (MF) on the surface and ends. Our calculations consider the exchange-correlation energies with the Hamprecht–Cohen–Tozer–Handy functional within the generalized gradient approximation (HCTH-GGA) and the double polarized DNP base function. The geometry optimization follows the minimum energy criterion for all six geometries we have considered. Results show that the MF is adsorbed through the groups NH₂–NH at one end of the nanotube. The system polarity is increased which indicates the possible dispersion and solubility. Moreover the interaction between these species induces an increase in the chemical reactivity of the order of 0.42 eV. Meanwhile the solvation in water keeps the semiconductor characteristics of both nanotube and MF. The work function of the BNNT-MF is drastically reduced respect to the pristine system when the BN nanotube is doped at its surface and ends with carbon. This means that the functionalized BN nanotube facilitates conditions to improve field emission.     

微芯片毛细管电泳法快速测定盐酸二甲双胍

提出用带有非接触电导检测的微芯片毛细管电泳法快速测定片剂中盐酸二甲双胍的含量。取盐酸二甲双胍片20片,剥除糖衣后混匀研细,称取0.100 0g,用水超声溶解、过滤,滤液定容至100mL供毛细管电泳分析。十字通道芯片使用前按规定进行清洗。试验中采用含5%(体积分数)乙醇和0.1mmol·L-1十二烷基磺酸钠的2.0mmol·L-1柠檬酸缓冲溶液作为分离介质,进时间为10.0s,分离电压为1.3kV,可在1min内实现分离和测定。盐酸二甲双胍的质量浓度在10.0~110.0mg·L-1范围内与相应峰高呈线性关系,检出限(3S/N)为1.0mg·L-1。应用此方法分析了3个片剂样品,并用标准加入法做回收试验,测得回收率在94.5%~103%之间,测定值的相对标准偏差(n=6)在0.63%~1.1%之间。     

二甲双胍化学反应性的密度泛函理论研究及实验研究

二甲双胍(MET)是一个非常优良的降血糖药,一直是治疗II型糖尿病(T2DM)的首选药物,但其脂溶性较差,也存在引起胃肠道不适等副作用,对其结构修饰和衍生化,特别是将其研制成前药(Prodrug)具有一定的临床意义。为了探明二甲双胍化学反应的性能特点,本文基于密度泛函理论（DFT）开展了二甲双胍的化学内禀性质研究,包括各种可能互变异构体的单点能和量子化学反应性指数。此外,还对各异构体互变过程的过渡态以及它们的反应路径进行了研究。在此基础上,本文还对二甲双胍与亲电试剂的化学反应机理进行了初探,并用化学合成反应来验证,从而让我们能够从理论上弄清楚二甲双胍化学反应的特殊性质。     

Nickel oxide nanotubes-carbon microparticles/Nafion nanocomposite for the electrooxidation and sensitive detection of metformin

The electrocatalytic oxidation of metformin was studied on a nickel oxide nanotubes-carbon microparticles/Nafion nanocomposite, using cyclic voltammetry and chronoamperometry. In the presence of metformin, the anodic peak current of the Ni(II)/Ni(III) transition increased, followed by a decrease in the corresponding cathodic currents. Based on the results, the drug was oxidized on nickel oxide nanotubes via an electrocatalytic mechanism. The catalytic rate constant, the electron transfer coefficient and the diffusion coefficient involved in the electrocatalytic oxidation of the drug were reported. A sensitive and efficient amperometric method was presented for the analysis of the drug, and the corresponding analytical parameters were reported. For metformin, a detection limit of 0.45 μmol L⁻¹ was obtained. The proposed amperometric method was also applied to the analysis of commercial tablets and the results were in good agreement with the declared values. Also, the applicability of the method to the direct assays of the drug in human serum and urine and breast milk was described.     

基于分子印迹聚合物的化学发光传感器测定尿样中的甲福明

合成了甲福明的分子印迹聚合物,以此聚合物为识别物质,在线分离富集甲福明,建立了一种测定甲福明的流动式化学发光但感器。N-溴代丁二酰亚胺(NBS)和荧光素与甲福明发生化学反应,产生强的化学发光。甲福明质量浓度在2×10-8~8×10-6g/mL范围内同发光强度成良好线性关系,方法的检出限为6×10-9g/mL,相对标准偏差小于5%(n=9)。选择性实验表明将分子印迹聚合物作为识别物质应用于化学发光分析中,能大大提高化学发光分析方法的选择性。该传感器可逆性强、稳定性好,可重复使用100次以上,已用于人体尿样中甲福明的测定。     

Simultaneous Determination of Metformin Hydrochloride, Cyanoguanidine and Melamine in Tablets by Mixed-Mode HILIC

A simple and specific hydrophilic interaction liquid chromatography (HILIC) procedure for the quantification of metformin hydrochloride (MFH) and its impurities in bulk pharmaceuticals and finished dosage forms has been developed. The method is based on hydrophilic interaction of the analytes with silica. The influence of the weaker solvent, acetonitrile, pH and the nature and ionic strength of the buffer was studied. Linearity range and percent recoveries for MFH were 100–400 μg mL⁻¹ and 100.62%, respectively. Good validation data were obtained for all compounds. The method separates impurities cyanoguanidine (CGD), melamine (MLN) and other degradation products with a run time of less than 13 min. Degradation studies involved thermal stress, hydrolysis at various pHs and chemical and photolytic oxidation.     

Determination of Metformin in Human Plasma by Liquid Chromatography-tandem Mass Spectrometric Assay

Introduction Metformin (1,1-dimethylbiguanide) (Fig. 1) is an oral anti-hyperglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus (type Ⅱ). Owing to its weight-decreasing and serum lipid-normalizing effects, it is especially recommended for obese patients[1,2] Various analytical methods have been described for the measurement of metformin in biological fluids, including gas chromatography(GC)[3-5], capillary electrophoresis (CE)[6] and HPLC[7～16]with UV detection[7-12,17] HPLC-Mass spectrometry (LC/APCIMS/MS ) offers an attractive alternative to HPLC[18].     

Simultaneous analysis of metformin and cyanoguanidine by capillary zone electrophoresis and its application in a stability study

A capillary zone electrophoresis method was established for stability study of metformin (MET). MET and cyanoguanidine (CGN; a major degradation product) were well separated (with a resolution of 38.9) in 40 mM citrate buffer (pH 6.7) using a fused‐silica capillary with an effective length of 60 cm and an inner diameter of 50 μm, injection at 50 mbar for 5 s at 30°C with an applied voltage of 15 kV and diode array detection at 214 nm. Method validation showed good linearity (r² > 0.99), precision (%RSDs < 1.98%), and accuracy (%recovery between 98.3 and 100.9%). Limits of detection and quantification were <30 and 100 μg/mL, respectively. The method was robust upon alteration of pH and voltage (%RSDs < 1.99%). Stability profiles of metformin from 11 stress conditions and the degradation kinetics could be established, using the simple capillary zone electrophoresis system. A mechanism for the degradation of MET was also proposed. MET was stable in neutral hydrolysis, but degraded under alkaline hydrolysis and oxidation. Under both conditions, CGN was quantified as the degradation product. An assay of MET in raw material and tablets showed that content of the drugs in all samples met the requirements of pharmacopeias and CGN was not detected.     

曙红Y探针共振瑞利散射法测定盐酸二甲双胍

在pH=3.0的B-R缓冲介质中,盐酸二甲双胍(MFH)与曙红Y(EY)形成离子缔合物,引起共振瑞利散射光谱显著增强,其最大特征散射波长位于292nm处。MFH的浓度在0.05~2.5μg/mL范围内与散射信号的增强(△I_(RRS))呈线性关系。MFH的检出限(3σ)为0.02μg/mL。讨论了适宜的反应条件和共存物质的影响。据此,提出了测定痕量MFH的光散射新方法,并应用于实际样品中MFH的测定,结果满意。