Stability-indicating spectrophotometric methods for determination of tazarotene in the presence of its alkaline degradation product by derivative spectrophotometric techniques

The stability of tazarotene (TZ) was investigated and two stability‐indicating methods—namely, first derivative and a derivative ratio spectrophotometric method—were used to determine tazarotene in the presence of its alkaline degradation product (HD) using methanol as a solvent. A linear relationship was obtained in the range 1–10 µg ml⁻¹ for both methods. By applying the proposed methods, it was possible to determine tazarotene in its pure powdered from with accuracy 99.35 ± 1.410 (n = 10) for the first derivative method and 99.45 ± 1.053 (n = 10) for the derivative ratio method. First derivative and derivative ratio methods were used for the analysis of laboratory‐prepared mixtures containing different ratios of tazarotene and its degradation product and they were valid in the presence of up to 70% and 80% degradation product, respectively. The proposed methods were validated and found to be suitable as stability‐indicating assay methods for tazarotene in pharmaceutical formulations. Copyright © 2010 John Wiley & Sons, Ltd.     

洛伐他汀联御旨必妥治疗高脂血症的临床应用价值

目的探讨洛伐他汀联合脂必妥治疗高脂血症的临床价值。方法将我中心2012年1月～2013年5月收治的高脂血症患者168例按不同治疗方法分为实验组（洛伐他汀＋脂必妥）和对照组（洛伐他汀）,均治疗8周后对两组患者的治疗效果进行综合比较。结果实验组总有效率为90．47％,明显优于对照组的75．00％（P〈0．05）,实验组的总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL—C）、TC—HDL—C／HDL—C均较对照组明显降低（P〈0．05）,高密度脂蛋白胆固醇（HDL—C）较对照组明显升高（P〈0．05）。结论洛伐他汀联合脂必妥治疗高脂血症的临床效果显著,且有较高安全性,值得临床推广应用。     

HPLC and chemometric assisted spectrophotometric methods for simultaneous determination of diprophylline, phenobarbitone and papaverine hydrochloride

Three methods are developed for the simultaneous determination of diprophylline (DP), phenobarbitone (PH) and papaverine hydrochloride (PP). The chromatographic method depends on a high performance liquid chromatographic (HPLC) separation on a reversed-phase C18 column with a mobile phase consisting of 0.02 M potassium dihydrogen phosphate, pH 3.5--acetonitrile (55:45 v/v). Quantitation was achieved with UV detection at 210 nm based on peak area. The other two chemometric methods applied were principal component regression (PCR) and partial least squares (PLS-1). These approaches were successfully applied to quantify the three drugs in the mixture using the information included in the UV absorption spectra of appropriate solutions in the range 215-245 nm with the intervals Delta lambda = 0.2 nm. The calibration PCR and PLS-1 models were evaluated by internal validation (prediction of compounds in its own designed training set of calibration), by cross-validation (obtaining statistical parameters that show the efficiency for a calibration fit model) and by external validation over laboratory-prepared mixtures and pharmaceutical preparations. The PCR and PLS-1 methods require neither any separation step, nor any priori graphical treatment of the overlapping spectra of the three drugs in a mixture. The results of PCR and PLS-1 methods were compared with HPLC method obtained in pharmaceutical formulation and a good agreement was found.     

Comparison of derivative spectrophotometric and liquid chromatographic methods for the determination of rofecoxib

Two different UV spectrophotometric methods were developed for the determination of rofecoxib in bulk form and in pharmaceutical formulations. The first method, an UV spectrophotometric procedure, was based on the linear relationship between the rofecoxib concentration and the lambdamax amplitude at 279 nm. The second one, the first derivative spectrophotometry, was based on the linear relationship between the rofecoxib concentration and the first derivative amplitude at 228, 256 and 308 nm. Calibration curves were linear in the concentration range using peak to zero 1.5-35.0 microg x ml(-1). HPLC was carried out at 225 nm with a partisil 5 ODS (3) column and a mobile phase constituted of acetonitrile and water (50 :50 v/v). A linear range was found to be 0.05-35.0 microg x ml(-1). The developed methods were successfully applied for the assay of pharmaceutical dosage form. The statistics of the analytical data is also presented. The results obtained by first derivative spectrophotometry were compared with HPLC and no significant difference was found.     

HPLC法测定山楂红曲胶囊中洛伐他汀

目的 建立山楂红曲胶囊中洛伐他汀的处理及含量测定方法。方法 色谱柱为Kromasil C₁₈柱（250 mm×4.6 mm,5μm）,紫外检测波长238 nm,柱温25℃,体积流量1.0 mL/min,流动相为甲醇：0.1%磷酸溶液（75：25）。结果 洛伐他汀质量浓度在2.04~306 μg/mL与峰面积线性关系良好,平均回收率为98.58%,RSD=1.12%（n=9）。结论 该方法准确、简便,可用于山楂红曲胶囊的质量控制。     

Comparison of two derivative spectrophotometric methods for the determination of alpha-tocopherol in pharmaceutical preparations

Simple, sensitive and reliable derivative spectrophotometric methods were developed and validated for determination of alpha-tocopherol in pharmaceutical preparations. The solutions of standard and the sample were prepared in absolute ethanol. The quantitative determination of the drug was carried out using the first derivative values measured at 284, 304 nm and the second derivative values measured at 288, 296 nm. Calibration graphs constructed at their wavelengths of determination were linear in the concentration range of alpha-tocopherol using peak to zero 10-250 microg ml(-1) for first and second derivative spectrophotometric methods. Developed spectrophotometric methods in this study are accurate, sensitive, precise, reproducible, and can be directly and easily applied to Evon dragee form as pharmaceutical preparation. Statistical analysis (Student's t-test) of the obtained results showed no significant difference between the proposed two methods.     

洛伐他汀联合异烟肼、利福平、吡嗪酰胺致大鼠肝损伤的实验研究

目的 探讨洛伐他汀联合异烟肼(H)、利福平(R)、吡嗪酰胺(Z)(联用简称为HRZ)致大鼠肝损伤的特点.方法 SPF级8周龄SD大鼠80只,雌雄各半,采用随机数字表法随机分为四组:空白对照组、洛伐他汀组、HRZ组、洛伐他汀+HRZ组,按人-鼠间药物剂量换算,分别给予相应药物灌胃,于10、35、55 d分别处死大鼠,采集标本行肝功能生化指标、肝病理学检测及电镜观察.结果 在给药10、35、55 d时,与空白对照组比较,洛伐他汀+HRZ组肝功能生化指标均明显升高,总胆红素(TBil)、直接胆红素(DBil)、间接胆红素(IBil)升高,差异有统计学意义,而天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、碱性磷酸酶(ALP)升高,差异无统计学意义,且随着给药时间点延长,洛伐他汀+HRZ组肝损伤并未呈进行性增加;与洛伐他汀组、HRZ组两两比较时,仅AST在给药55 d时洛伐他汀组与HRZ组比较差异有统计学意义,其他各组在各时间点两两比较均差异无统计学意义;以上结果与病理、电镜观察结果一致.结论 洛伐他汀联合HRZ后短时间内即可能出现肝损伤,以胆汁淤积型肝损伤为主;且随着给药时间延长,洛伐他汀联合HRZ所致肝损伤可能存在适应性现象,联合组并未比洛伐他汀单用或HRZ单用更容易导致肝损伤.     

Direct spectrophotometric determination of quercetin in the presence of ascorbic acid

The current research provides a simplified sample preparation procedure for the accurate estimation of quercetin in pure and in the pharmaceutical dosage form. Direct spectrophotometric method for the determination of quercetin in the presence of ascorbic acid was established. The influences of medium, wavelength, pH, temperature and the ionic strengths on quercetin determination were investigated. The best conditions for calibration curve are: 50% ethanol, lambda = 370 nm, pH = 4.2, T = 34 degrees C and I = 7.5 x 10(-5) M. Beer's law is obeyed in the concentration range 1.0-12.0 microg ml(-1) for quercetin. The corresponding detection limit is 0.76 microg ml(-1). The proposed method was verified by analyzing Quercetin + C capsules, Twinlab.     

A new spectrophotometric method for the determination of methyldopa

A new, simple and low cost spectrophotometric method for the determination of methyldopa in pharmaceutical preparations was developed. The method was based on the coupling of methyldopa with 2,6-dichloroquinone-4-chlorimide (DCQ). The absorbance maximum (λ_max) of the resulted colored product was at 400 nm. Different buffers were used to determine the optimal pH for the reaction. About 1% w/v acetate buffer with pH 8.0 gave the optimal pH required for the reaction. Of the different solvents tried, water and ethanol were found to be the most suitable solvents. Beer’s law was obeyed in concentration range of 4–20 μg/ml methyldopa. The correlation coefficient was found to be (r = 0.9975). The limit of detection and limit of quantification were 1.1 μg/ml and 3.21 μg/ml, respectively. The reaction ratio between methyldopa and DCQ was studied and found to be 1:3. The work included the study of the possible interference of hydrochlorothiazide found in combination with methyldopa tablets. The method was validated and results obtained for the assay of two different brands of methyldopa tablets were compared with the BP method (colorimetric). The repeatability and reproducibility of the developed method were evaluated and the obtained results quoted. The derivative formed as a result of the reaction of methyldopa with DCQ was isolated and its possible mechanistic pathway was suggested.     

七叶皂苷对洛伐他汀在高脂血症大鼠模型体内药代动力学的影响

目的在高脂血症大鼠模型中研究七叶皂苷对洛伐他汀药代动力学的影响。方法采用高脂饲料喂饲大鼠,构建高脂血症大鼠模型,通过血清生化分析确定造模成功。选择12只造模成功的大鼠,随机分成2组,即单独给药组和联合给药组,每组6只大鼠。单独给药组和联合给药组大鼠分别经尾静脉注射给予0.9%生理盐水和注射用七叶皂苷钠(0.5 mg/kg,qd),连续14 d。第14天,给药后,两组大鼠灌胃给予洛伐他汀(20 mg/kg,0.5%CMC-Na溶液),并于洛伐他汀给药前和给药后不同时间点采集血样,采用HPLC-MS/MS方法测定洛伐他汀及其活性代谢物洛伐他汀酸的血药浓度,计算药动学参数。结果长期给予七叶皂苷钠导致洛伐他汀酸的血浆暴露水平显著升高,Cmax、AUC0-t、AUC0-∞分别是单独给药组的2.43(90%CI:1.55,3.31)、2.66(90%CI:1.67,3.66)和2.99倍(90%CI:1.44,4.55),两组比较差异有统计学意义(P<0.05)。与单独给药组相比,联合给药组洛伐他汀的血浆暴露也略有增加,但两组Cmax和AUC比较差异无统计学意义(P>0.05)。结论七叶皂苷可抑制高脂血症模型大鼠的洛伐他汀代谢,增加其体内暴露水平。     

Validation of simultaneous volumetric and spectrophotometric methods for the determination of captopril in pharmaceutical formulations

Simple, sensitive and economical simultaneous volumetric and spectrophotometric methods for the determination of captopril have been developed. The methods were based on the reaction of captopril with potassium iodate in HCl medium. Amaranth was used as indicator to detect the end-point of the titration in aqueous layer. The iodine formed during the titration was extracted into CCl4 and subsequently determined spectrophotometrically at 510 nm. The Beer's law was obeyed in the concentration range of 120-520 microg ml-1. Rigorous statistical analyses were performed for the validation of the proposed methods. The proposed methods were successfully applied to the determination of captopril in dosage forms. Comparison of the means of the proposed procedures with those of reference methods using point and interval hypothesis tests showed no statistically significant difference.     

以红曲为原料保健食品中洛伐他汀的含量测定

目的建立以红曲为原料的保健食品中总洛伐他汀含量测定的方法。方法用高效液相色谱法一次测定保健食品中两种结构形式洛伐他汀的总含量,色谱条件为：色谱柱（zorbaxC18,4.6×250mm,5μm）;流动相：甲醇-水-磷酸（385：115：0.14）;检测波长：238nm;流速：1.0mL/min。结果洛伐他汀在2.0～300μg/mL范围内线性关系良好,r=0.9999;平均回收率为99.5%,RSD为0.57%（n=9）。结论该高效液相色谱法简单、灵敏、快速、准确,适用于以红曲为原料的保健食品中总洛伐他汀的含量测定。     

Three new spectrophotometric methods applied to the simultaneous determination of hydrochlorothiazide and irbesartan

This work involves the simultaneous determination of hydrochlorothiazide and irbesartan in a binary mixture without previous separation by three new analytical methods. The first method, based on compensation technique, is presented for the derivative spectrophotometric determination of binary mixtures with overlapping spectra. By using ratios of the derivative maxima or the derivative minimum, the exact contribution of either component in the binary mixture can be measured and the amounts quantified. The second method uses of the first derivative of the ratio spectra. The ratio spectra were obtained by dividing the absorption spectra of the binary mixture by that of one of the components. The amplitudes in the first derivative of the ratio spectra at 231, 266, 279, 238 and 248 nm were selected to determine hydrochlorothiazide and irbesartan in binary mixtures. The concentration of the other components are then determined from their respective calibration graphs treated similarly. With the third method, the absorbance ratio method, the determination of hydrochlorothiazide and irbesartan was performed using the absorbances read at 272 nm, 241 nm and 263 nm in the zero-order spectra of their mixture. The absorbance ratio was also developed as a comparison method. The three methods are simple, accurate, rapid and require no preliminary separation steps and can, therefore, be used for routine analysis of both drugs in quality control laboratories.     

Simultaneous determination of montelukast and loratadine by HPLC and derivative spectrophotometric methods

In this study, high performance liquid chromatography (HPLC) and second derivative spectrophotometry have been used and described for the simultaneous determination of montelukast and loratadine in pharmaceutical formulations. HPLC separation was achieved with a Symmetry C18 column and sodium phosphate buffer (pH adjusted to 3.7): acetonitrile (20:80, v/v) as eluent, at a flow rate of 1.0 ml/min. UV detection was performed at 225 nm. The LC method is simple, rapid, selective and stability indicating for the determination of montelukast. 5-Methyl 2-nitrophenol was used as internal standard for the purpose of quantification of both the drugs in HPLC. In the second-order derivative spectrophotometry, for the determination of loratadine the zero-crossing technique was applied at 276.1 nm, but for montelukast peak amplitude at 359.7 nm (tangent method) was used. Both methods were fully validated and a comparison was made for assay determination of selected drugs in formulations. The results confirm that the methods are highly suitable for its intended purpose.     

Flow-injection spectrophotometric methods for the determination of tenoxicam

Two sensitive and rapid flow-injection spectrophotometric methods are proposed for the determination of tenoxicam (TX). In the first method, a Fe(III)-tenoxicam complex is formed in a methanolic medium and the absorbance is measured at 540 nm, while the second method involves measurement of the absorbance at 355 nm of a solution containing the drug in hydrochloric acid medium. In both methods, the peak heights were proportional to tenoxicam concentration over the ranges 7.0-320 and 0.5-8.5 mg/l(-1), respectively. The methods have been applied to the routine determination of the drug in dosage forms.     

洛伐他汀对冠心病合并高脂血症的疗效分析

目的：对应用洛伐他汀治疗冠心病伴高脂血症的疗效进行观察,探讨这种降脂疗法的疗效及其副作用。方法：选择冠心病合并高脂血症患者50例,在冠心病基础治疗上,给予洛伐他汀30mg口服,1次/d,每晚饭后顿服,1个疗程12周。检测血脂中胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）水平,记录服药期间不良反应,比较观察期间心绞痛、心肌梗死的发生率。结果：治疗后,患者TC、TG、LDL-C水平均有明显降低（P〈0.05）,HDL-C明显升高（P〈0.05）。降低TC、TG、LDL-C总有效率分别为88%、64%、80%,升高HDL-C总有效率为66%;TC、TG、LDL-C的达标率分别为62%、44%、66%。患者对药物均有良好的耐受性,无因不良反应退出观察者。结论：洛伐他汀对降脂和预防冠心病疗效显著,价格相对低廉,服用方便,值得在基层医院推广应用。     

Simultaneous spectrophotometric determination of mefenamic acid and paracetamol in a pharmaceutical preparation using ratio spectra derivative spectrophotometry and chemometric methods

Four new methods are described for the simultaneous determination of mefenamic acid (MEF) and paracetamol (PAR) in their combination. In the first method, ratio spectra derivative method, analytical signals were measured at the wavelengths corresponding to either maximums or minimums for both drugs in the first derivative spectra of the ratio spectra obtained by dividing the standard spectrum of one of two drugs in 0.1 M NaOH:methanol (1:9). In the chemometric techniques, classical least-squares, inverse least-squares and principal component regression (PCR), the training was randomly prepared by using the different mixture compositions containing two drugs in 0.1 M NaOH:methanol (1:9). The absorbance data was obtained by the measurements at 13 points in the wavelength range 235–355 nm in the absorption spectra. Chemometric calibrations were constructed by the absorbance data and training set for the prediction of the amount of MEF and PAR in samples. In the third chemometric method, PCR, the covariance matrix corresponding to the absorbance data was calculated for the basis vectors and matrix containing the new coordinates. The obtained calibration was used to determine the title drugs in their mixture. Linearity range in all the methods was found to be 2–10 μg/ml of MEF and 4–20 μg/ml of PAR. Mean recoveries were found satisfactory (>99%). The procedures do not require any separation step. These methods were successfully applied to a pharmaceutical formulation, tablet, and the results were compared with each other.     

HPLC and chemometric-assisted spectrophotometric methods for simultaneous determination of atenolol, amiloride hydrochloride and chlorthalidone

Three methods are presented for the simultaneous determination of atenolol (AT), amiloride hydrochloride (AM) and chlorthalidone (CD). The high performance liquid chromatographic (HPLC) method depends on the separation of each drug on a reversed phase, RP (18) column. Elution was carried out with a mobile phase consisting of acetonitrile -5mM heptansulphonic acid sodium salt (20:80, v/v, pH 4.4). Quantitation was achieved with UV detection at 274 nm based on peak area. The other two-chemometric-assisted spectrophotometric methods applied were principal component regression (PCR) and partial least squares (PLS-1). These approaches were successfully applied to quantify each drug in the mixture using the information included in the absorption spectra of appropriate solutions in the range 240-290 nm with the intervals Deltalambda=0.2 nm. The three methods were successfully applied to a pharmaceutical formulation (tablets), and the results were compared with each other.     

洛伐他汀的杂质研究

目的从洛伐他汀结晶母液中分离纯化杂质成分,并进行结构鉴定。方法采用硅胶柱色谱、硅胶制备TLC、反相硅胶柱色谱、半制备HPLC等方法进行分离纯化;通过NMR、MS进行结构解析。结果分离得到6个单体化合物,分别鉴定为脱水Monacolin L,脱水二氢洛伐他汀,Monacolin L酸,Monacolin L酸甲酯,二氢洛伐他汀和二氢洛伐他汀酸。结论脱水Monacolin L为一新化合物。