Simultaneous determination of sulfamethoxazole and trimethoprim in microgram quantities from low plasma volume by liquid chromatography–tandem mass spectrometry

A highly sensitive, selective and high-throughput liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for simultaneous quantification of sulfamethoxazole (SMZ) and trimethoprim (TMP) has been developed and validated using imipramine as an internal standard. The analytes were extracted from 50 µL human plasma using solid phase extraction (SPE) and separated on Thermo Hypersil Gold C18 (50 mm × 4.6 mm, 5 μm) column under isocratic conditions in a run time of 2.5 min. Detection was carried out by tandem mass spectrometer, interfaced with electro spray ionization and operating in positive ionization mode. The calibration curves were linear over the concentration range of 0.88–80 µg/mL for SMZ and 0.03–30 µg/mL for TMP. The intra- and inter-day accuracy and precision (% CV) evaluated at four quality control levels were within 93.5–105.0% and 1.3–7.2% respectively. The absolute recovery was greater than 81% for both the analytes at two concentration levels. Stability of SMZ and TMP was assessed under different storage conditions. The validated method was successfully applied for a bioavailability study in 12 healthy volunteers after oral administration of 800 mg of SMZ and 160 mg of TMP succinate tablet formulations under fasting condition.     

混合线性分析法的原理及应用

对一种新近发展的多元校正方法－混合线性分析法（hybrid linear analysis,HLA)的原理进行了深入探讨和阐述，用该法进行了模拟体系和复方头孢氨苄制剂的分析，在主因子数确定，单位谱的获得，波长选择、适用范围等方面进行了讨论。结果表明，HLA法可给出优于偏量小二乘法（PLS）的结果，方法易行，结果准确。在复杂体系分析中具有较好的应用前景。     

毛细管电泳-安培法测定复方磺胺甲噁唑片中的有效成分

采用毛细管电泳-安培法(CE-AD)同时分离测定了磺胺甲噁唑(sulfamethoxazole,SMZ)、磺胺嘧啶(sulfadiazine,SD)和抗菌增效剂甲氧苄胺嘧啶(trimethoprim,TMP)3种常用磺胺类抗菌药物成分,考察了实验参数对分离、检测体系的影响。在优化实验条件下,以300μm碳圆盘电极作为工作电极,检测电位为1050mV(vs.SCE),在Na2B4O7(13mmol/L)-KH2PO4(18mmol/L)(pH5.8)的缓冲溶液中,分离电压18kV,进样6s,3组分在14min内可实现基线分离。上述3组分浓度分别在5×10-4~5×10-2、5×10-4~0.1和5×10-4~5×10-2g/L范围内与其峰电流强度呈线性关系,检出限达5.1×10-5~8.0×10-5g/L(S/N=3)。该方法已成功应用于复方磺胺甲噁唑片中抗菌活性成分的含量测定,结果令人满意。     

紫外光谱净信号法测定酸性环境下复方磺胺甲噁唑片两个有效组分

被分析组分的光谱净信号将正交于其它药物组分和辅料光谱所张成的光谱子空间,从而消除其它组分对被分析组分的光谱干扰,此净信号将与被分析组分的浓度成正比,据此建立了药物制剂分析的净信号方法。本文利用该方法研究了在酸性条件下紫外光谱测定复方磺胺甲噁唑片的两种有效成分磺胺甲噁唑(SMZ)和甲氧苄啶(TMP)。SMZ和TMP的线性范围分别为0.48~7.84μg/mL(r=0.9981)和0.12~1.5μg/mL(r=0.9986),平均回收率分别为99.5%和101.0%,RSD分别为1.87%和3.60%。本法简便、快速和准确,可用于酸性条件下复方磺胺甲噁唑片中SMZ和TMP含量的快速、同时准确测定。     

类模板分子印迹整体柱测定甲氧苄啶的研究

利用三聚氰胺(MAM)与甲氧苄啶(TMP)分子中嘧啶环局部结构类似的特性,以三聚氰胺为类模板分子,甲基丙烯酸(MAA)为功能单体,二甲基丙烯酸乙二醇酯(EDMA)为交联剂,原位聚合法制备了对甲氧苄啶(TMP)有识别作用的分子印迹(MIP)整体柱.在优化的色谱条件下,该印迹整体柱对甲氧苄啶显示出选择性识别作用,而对叶酸、...     

甲氧苄啶修饰玻碳电极安培法对过氧化氢的测定

在0.1 mol·L~(-1) KNO_3底液中,研究了甲氧苄啶在玻碳电极上的电化学性质,发现在0.140、0.177 V处出现1对可逆的氧化还原峰.进一步用电化学沉积的方法将甲氧苄啶修饰在玻碳电极上,考察了各种实验条件对修饰电极性能的影响,并通过电子扫描显微镜和电化学阻抗谱对修饰电极的表面性质进行了表征,所制得的修饰电极对过氧化氢的还原有很好的催化作用.在-0.3 V的工作电位下,用计时安培法对过氧化氢进行了测定,过氧化氢的浓度在1.96×10~(-5) ～1.10×10~(-3) mol·L~(-1)范围内与响应电流呈线性关系,检出限为4.0 μmol·L~(-1).该修饰电极制作简单、使用寿命长,实际试样的回收率为97% ～104%.     

高效液相色谱-荧光-紫外法测定动物肌肉组织中多类药物残留

建立了同时检测动物肌肉组织中9种喹诺酮类药物、7种磺胺类药物和甲氧苄啶的高效液相色谱检测方法.动物肌肉组织样品用磷酸盐缓冲液提取,HLB固相萃取柱净化,洗脱液用氮气吹至近干,磷酸盐缓冲液复溶,以甲酸水溶液-乙腈体系为流动相,梯度洗脱,荧光-紫外检测器串联测定.本方法的线性良好,相关系数r>0.9987;平均回收率为70.6%～103.4%,相对标准偏差为1.2%～11.4%; 荧光检测器测定喹诺酮类药物的检出限为0.04～0.4 μg/kg;紫外检测器测定磺胺类药物和甲氧苄啶的检出限为3.5 μg/kg.本方法具有简便、通用性强的特点,适用于动物肌肉组织中上述药物的常规残留检测.     

Luminescent Terbium Protein Labels for Time‐Resolved Microscopy and Screening

Brilliance of terbium : Heterodimeric conjugates of trimethoprim covalently linked to sensitized terbium chelates bind to Escherichia coli dihydrofolate reductase fusion proteins with nanomolar affinity (see picture). Terbium luminescence enables sensitive and time‐resolved detection of labeled proteins in vitro and on the surface of living mammalian cells.

     

Metal-pyrimidine interaction: synthesis and crystal structure of a cadmium complex of trimethoprim ([CdBr2(TMP)2(H2O)2]·H2O, TMP = trimethoprim)

The crystal structure of a cadmium complex of trimethoprim ([CdBr₂(TMP)₂(H₂O)₂] · H₂O, TMP = trimethoprim) has been determined from X-ray diffraction data using MoK radiation. The crystals are monoclinic, C2/c, with a = 7.7811(11), b = 15.439(3) c = 29.645(6)Å, = 97.23(2)° and Z = 4. Trimethoprim (2,3-diamino(3,4,5trimethoxybenzyl)pyrimidine) acts as a monodentate ligand. Cadmium is coordinated to N(1) atoms of two trimethoprim moieties. The octahetral coordination geometry around cadmium is completed by two Br-ions and two water molecules. The complex has a two-fold axis coinciding with a crystallographic two-fold axis. There is an interligand hydrogen bond between the bromide ion and the 2-amino group of the pyrimidine.     

固相萃取法对微量药物的选择性富集和直接测定

选用能够识别抗菌药物氧苄氨嘧啶（ＴＭＰ）的模权聚合物作固相萃取剂,从稀溶液中可选择性地富集ＴＭＰ,在生理浓度下,富集因数为３５．７,而非模板事物无富集能力。在洗脱过程中直接用于ＴＭＰ的测定,不需要随后的色谱分析手续。基于此,建立了一个样品富集和测定的新方法,方便简单可靠,用于尿样中低２的ＴＭＰ的测定,回收率达到９１．７％,结果满意。