分光光度法测定替米沙坦

用分光光度法研究了替米沙坦与茜素的荷移反应,提出了测定替米沙坦的荷移分光光度法。在丙酮溶剂中,替米沙坦和茜素形成的络合物的最大吸收波长为548nm,两者的组成比为1比2。替米沙坦质量浓度在16～240mg·L-1范围内服从比耳定律,表观摩尔吸光率为2.34×103L.mol-1.cm-1。采用此法分别测定了替米沙坦胶囊和片剂中替米沙坦的含量,所得测定值与文献报道值相符。用标准加入法做方法的精密度和回收试验,测得回收率为99.5%(胶囊)和99.8%(片剂)。     

酚红分光光度法测定替米沙坦的含量

在pH为7.9的B-R缓冲体系中,酚红与替米沙坦作用,形成离子缔合物,溶液颜色发生改变,其最大显色和褪色波长分别为558,426 nm,替米沙坦的浓度与溶液的增色或褪色呈线性关系,建立了分光光度法测定替米沙坦的含量。在最大显色和褪色波长处,替米沙坦的浓度分别在6.50×10~(-7)～1.35×10~(-5)mol·L~(-1)和7.50×10~(-7)～1.00×10~(-5)mol·L~(-1)范围内遵守比耳定律,摩尔吸光率分别为6.59×10~4,2.12×10~4L·mol~(-1)·cm~(-1),检出限(3δ)分别为1.72×10~(-7),8.53×10~(-7)mol·L~(-1)。用于血样、尿样和药品中替米沙坦的测定,相对标准偏差(n=11)在0.72%～2.56%之间。     

固绿FCF分光光度法测替米沙坦的含量

在pH6.2的Britton-Robinson缓冲介质中,替米沙坦(TMST)与生物染色剂固绿FCF(FGF)反应,形成离子缔合物,溶液颜色发生明显改变,最大正、负吸收波长分别位于598、632 nm,从而建立光度法测定替米沙坦.在598、632 nm处,替米沙坦分别在0～1.35×10-5mol/,L、0～1.05×...     

糖尿病患者尿液中常见药物含量的高效液相色谱法测定

建立了高效液相色谱/二极管阵列检测法同时测定糖尿病患者尿液中二甲双胍、格列吡嗪和替米沙坦3种常用药物含量的方法.室温条件下以2.5 mmol/L十二烷基硫酸钠-20 mmol/L磷酸二氢钠(pH 4.6)-乙腈为流动相,梯度洗脱,实现了3种药物的有效分离.采用3种不同检测波长,测得二甲双胍、格列吡嗪和替米沙坦的检出限分...     

偶氮氯膦Ⅰ分光光度法测定替米沙坦的含量

在pH=8.80的B-R弱碱性缓冲介质中,替米沙坦与偶氮氯膦Ⅰ染料反应形成离子缔合物,溶液颜色发生明显改变,最大吸收波长在558nm处,替米沙坦的浓度与溶液的变色程度呈良好的线性关系,从而建立了测定替米沙坦含量的光度法。在最大吸收波长处,替米沙坦的浓度在0～8.1×10-6mol/L范围内遵守比耳定律,表观摩尔吸光系数ε558为1.84×104L·mol-1·cm-1,检出限为8.63×10-7mol/L,研究了适宜的反应条件及影响因素。方法具有较高的灵敏度和良好的选择性,可用于市售药品、尿液及血浆中替米沙坦的测定。     

基于文献计量学的化学抗高血压药物替米沙坦的可视化分析和趋势探索

基于文献计量学方法和CiteSpace、Vosviewer可视化软件分析我国2004年11月-2023年11月替米沙坦领域研究的作者、机构合作情况,从关键词频次、关键词聚类和关键词突现分析3个层面对这一领域的研究热点和发展脉络进行分析。研究结果表明,该领域的研究热点主要围绕血管紧张素Ⅱ受体拮抗剂（ARB）类药物、其它类型高血压药物、ARB类药物新应用、高血压常见并发症以及替米沙坦药效评价等研究。通过应用共聚物化工合成工艺,提高替米沙坦的药效;合成替米沙坦的药物共晶体以及开发新的药物靶点以扩大替米沙坦的适应症范围,并进一步优化其疗效成为该药物持续研究的前沿方向。这些研究方向为替米沙坦的发展提供了新的机遇和挑战,有望为临床应用提供更加有效和个性化的治疗策略。     

高效液相色谱-四极杆/线性离子阱质谱测定替米沙坦中N-甲基邻苯二胺残留量

建立了高效液相色谱-四极杆/线性离子阱质谱(HPLC-QTRAP-MS/MS)测定替米沙坦中N-甲基邻苯二胺残留量的分析方法。替米沙坦药物以水-乙腈(80∶20,体积比)溶解后,采用Agilent Eclipse XDB-C18色谱柱(3.5μm,2.1 mm×100 mm)进行分离,以0.1%(体积分数)甲酸水和乙腈作为流动相进行梯度洗脱,电喷雾正离子(ESI+)扫描方式下选择离子监测(SRM)模式对样品进行检测。结果表明,N-甲基邻苯二胺在2.0~50μg/L范围内线性关系良好(r0.99),检出限(S/N=3)为0.5μg/L,定量下限(S/N=10)为2.0μg/L。该方法操作简单、灵敏度高、重现性好,可用于替米沙坦中N-甲基邻苯二胺残留量的测定。     

替米沙坦及其类似物的合成和生物活性研究

设计合成了替米沙坦及其类似物, 改进了替米沙坦的合成工艺. 用邻苯二胺与相应的有机羧酸缩合, 所得产物苯并咪唑衍生物与4'-溴甲基联苯-2-甲酸甲酯通过N-烷基化得到相应的目标化合物, 合成了替米沙坦和9种未见文献报道的苯并咪唑联苯化合物, 其结构经¹H NMR, IR, MS和元素分析确证. 用体外动脉环的方法, 研究目标化合物的初步体外抗高血压活性, 试验结果表明其中部分化合物具有一定的抗高血压活性.     

甲酚红分光光度法测定替米沙坦的含量

在pH为6.60的B-R缓冲介质中,替米沙坦(TMST)与甲酚红反应生成离子缔合物。当以试剂空白作参比时,在572nm及428nm波长处分别有正、负吸收峰。测定在572nm处增色反应的吸光度或在428nm处褪色反应的吸光度均与TMST的浓度之间呈线性关系,可作为测定TMST的基础。在所提出的方法中采用572nm作为测定TMST的检测波长。在此条件下TMST的浓度在4.6×10-7～1.3×10-5 mol.L-1之间与所测吸光度呈线性关系,其表观摩尔吸光率为5.34×104L.mol-1.cm-1。应用此方法测定了TMST胶囊和片剂中TMST的含量,测定结果与标示量相符,测定值的相对标准偏差(n=11)均小于2.5%。     

三维荧光二阶校正同时测定人体液中伊立替康及其代谢物7-乙基-10-羟基喜树碱的含量

提出了激发发射矩阵荧光光谱与化学计量学二阶校正方法相结合用于同时快速定量人体液(血浆和尿液)中的伊立替康(CPT11)和其主要代谢产物7-乙基-10-羟基喜树碱(SN38)的绿色、高灵敏分析策略. 尽管其分析物之间以及分析物和背景之间的光谱存在严重重叠现象, 采用基于交替归一加权残差(ANWE)算法的二阶校正方法进行解析仍能得到令人满意的定性定量分析结果. 当该体系的组分数选取为3时, 可以得到血浆和尿液中CPT11的平均回收率分别为(96.8±6.3)%和(101.7±1.1)%, SN38在血浆和尿液中的平均回收率分别为(100.4±4.9)%和(101.6±1.1)%. 另外, 通过品质因子, 如灵敏度(SEN)、选择性(SEL)、检测下限(LOD)和定量检测限(LOQ)评估了该方法的准确性. 实验结果表明, 该方法能以“数学分离”代替繁琐的“物理和化学分离”, 成功地解决实际复杂体系中内源干扰物质与分析物光谱重叠所引起的难分辨的问题, 可用于人体液中CPT11和SN38含量的直接快速定量测定.     

A Simple and Highly Selective Determination of Telmisartan at Sodium Dodecyl Sulfate Modified Pyrolytic Graphite Surface

A simple, facile, selective and cost effective electrochemical method is proposed for the determination of telmisartan (TMS); a drug used for hypertension. A sodium dodecyl sulfate (SDS) modified edge plane pyrolytic graphite (EPPG) is prepared by simple immersion of EPPG in SDS solution at concentration greater than critical micelle concentration (CMC). The modified sensor exhibited superior sensing properties towards the oxidation of TMS. The modified surface was characterized by using the Energy dispersive X‐ray analysis, Field Emission Scanning Electron Microscopy, Electrochemical Impedance Spectroscopy and cyclic voltammetry. The quantitative investigations of the TMS were performed by applying the square wave voltammetry. The micelles of SDS form a pseudo complex with cation radical of TMS and catalyse the oxidation. The proposed sensor shows the linear calibration plot in the concentration range of 5–100 μM with sensitivity 0.2983 μA/μM and the limit of the detection of the sensor was found to be 0.082 μM. The specificity of the developed sensor was also evaluated in the presence of commonly present interfering substances in biological samples. The amount of TMS excreted in urine of the patients undergoing treatment has also been determined. The proposed method can be effectively applied for the investigation of TMS in pharmaceutical formulations and biological samples.     

Development and validation of liquid chromatography–mass spectrometry method for the determination of telmisartan in human plasma

A sensitive liquid chromatographic–electrospray ionization mass spectrometric method was developed and validated for fast determination of telmisartan in human plasma. Plasma of 0.1 mL was deprotienated with methanol, centrifugation, evaporation to dryness and dissolving in mobile phase, samples were separated using a Hypersil-Keystone C18 reversed-phase column (150 mm × 2.1 mm i.d., 5 μm), together with a mobile phase containing of acetonitrile–10 mM ammonium acetate (42:58, v/v), 0.2% acetic acid and was isocratically eluted at a flow rate of 0.2 mL/min. Telmisartan and its internal standard, valsartan, were measured by electrospray ion source in positive selective ion monitoring mode. The method demonstrated linearity from 1 to 2000 ng/mL (r = 0.9988). The limit of quantification for telmisartan in plasma was 1 ng/mL with good accuracy and precision. The mean sample extract recovery of the method were higher than 82 and 78% for telmisartan and internal standard (IS), respectively. The within-run and between-run precision ranged from 3.4 to 8.9% and 5.9 to 11.2% (relative standard deviation, R.S.D.), respectively.     

Determination of telmisartan in human blood plasma: Part I: Immunoassay development

Telmisartan is an angiotensin II receptor antagonist and a known drug against high blood pressure. In this report, the development of a new and rapid analytical technique, an enzyme-linked immunosorbent assay (ELISA) for the determination of telmisartan in human blood plasma is described. The immunoassay is based on a conversion of 4-(N-methylhydrazino)-7-nitro-2,1,3-benzooxadiazole (MNBDH) to 4-(N-methylamino)-7-nitro-2,1,3-benzooxadiazole (MNBDA), which is detected by fluorescence spectroscopy. The limit of detection was 0.1 ng/mL, the limit of quantification was 0.3 ng/mL and the working range extended from 0.3 ng/mL to 300 ng/mL.     

Enhancement effect of sodium dodecyl benzene sulfonate (SDBS) and its application into voltammetric determination of telmisartan

A sensitive and rapid electrochemical method was developed for the determination of telmisartan based on the enhancement effect of sodium dodecyl benzene sulfonate (SDBS). In 0.1 mol L⁻¹ HClO₄ and in the presence of 7.5 × 10⁻⁵ mol L⁻¹ SDBS, a well-defined and sensitive oxidation peak was observed for telmisartan at the acetylene black (AB) paste electrode. However, the oxidation peak is poor-shaped and the peak current is very low in the absence of SDBS, suggesting that SDBS shows obvious enhancement effect for the determination of telmisartan. After all the experimental parameters were optimized, a sensitive and simple electrochemical method was developed for determining telmisartan. The oxidation peak current is proportional to the concentration of telmisartan over the range from 2.5 × 10⁻⁷ to 2.0 × 10⁻⁵ mol L⁻¹. The detection limit is 7.5 × 10⁻⁸ mol L⁻¹ after 2 min of accumulation. This new voltammetric method was successfully used to detect telmisartan in drugs.     

Development of a molecularly imprinted solid‐phase extraction sorbent for the selective extraction of telmisartan from human urine

A novel molecularly imprinted solid‐phase extraction with spectrofluorimetry method has been developed for the selective extraction of telmisartan from human urine. Molecularly imprinted polymers were prepared by a noncovalent imprinting approach through UV‐radical polymerization using telmisartan as a template molecule, 2‐dimethylamino ethyl methacrylate as a functional monomer, ethylene glycol dimethacrylate as a cross‐linker, N,N‐azobisisobutyronitrile as an initiator, chloroform as a porogen. Molecularly imprinted polymers and nonimprinted control polymer sorbents were dry‐packed into solid‐phase extraction cartridges, and eluates from cartridges were analyzed using a spectrofluorimeter. Limit of detection and limit of quantitation values were 11.0 and 36.0 ng/mL, respectively. A very high imprinting factor (16.1) was achieved and recovery values for the telmisartan spiked in human urine were in the range of 76.1–79.1%. In addition, relatively low within‐day (0.14–1.6%) and between‐day (0.11–1.31%) precision values were obtained. Valsartan was used to evaluate the selectivity of sorbent as well. As a result, a sensitive, selective, and simple molecularly imprinted solid‐phase extraction with spectrofluorimetry method has been developed and successfully applied to the direct determination telmisartan in human urine.     

Determination of telmisartan in human blood plasma: Part II: Liquid chromatography-tandem mass spectrometry method development, comparison to immunoassay and pharmacokinetic study

A new liquid chromatography/atmospheric pressure chemical ionization-tandem mass spectrometry (LC/APCI-MS/MS) method with on-line sample clean-up for the determination of telmisartan in human blood plasma is presented. This technique is compared to a previously introduced enzyme-linked immunosorbent assay (ELISA), where fluorescence is used as detection method. For the LC/MS method applying an internal calibration via a deuterated internal standard, the limit of detection was 0.3 ng/mL, the limit of quantification was 0.9 ng/mL and the linear range extended from 0.9 to 1000 ng/mL. Forty-eight plasma samples from four healthy volunteers were analyzed in a pharmacokinetic study to obtain data for the method comparison. As a result, these two new and independent analytical methods for the determination of telmisartan in human blood plasma proved to yield comparable results for the amount of analyte.     

Simultaneous determination of ramipril, ramiprilat and telmisartan in human plasma using liquid chromatography tandem mass spectrometry

A rapid and sensitive liquid chromatography tandem mass spectrometry method has been developed and validated for the simultaneous determination of ramipril, ramiprilat and telmisartan in human plasma. The solid-phase extraction technique was used for the extraction of ramipril, ramiprilat and telmisartan from human plasma. Trandolaprilat and hydrochlorothiazide were used as the internal standards (ISs). Chromatography was performed on a Hypurity C18, 5 μm, 50 mm × 4.6 mm column, with the mobile phase consisting of ammonium acetate and acetonitrile (in a 20:80 ratio), followed by detection using mass spectrometry. The method involves a simple reversed isocratic chromatography condition and mass spectrometry detection, which enables detection at sub-nanogram levels. The method was validated and the lower limit of quantification for ramipril, ramiprilat and telmisartan was found to be 0.1 ng mL⁻¹, 0.1 ng mL⁻¹ and 2 ng mL⁻¹, respectively. The mean recovery for ramipril, ramiprilat and telmisartan ranged from 90.1 to 104.1%. This method increased the sensitivity and selectivity; resulting in high-throughput analysis of ramipril, ramiprilat and telmisartan using two different ISs in a single experiment for bioequivalence studies, with a chromatographic run time of 1.5 min only.