Quantitative analysis of bucillamine and its pharmaceutical formulation using FT-IR spectroscopy

A Fourier transform infrared (FT-IR) spectrometric method was developed for the rapid, direct measurement of bucillamine. Conventional KBr-spectra and DRIFTS spectra were compared for best determination of active substance in its tablet formulation. Two chemometric approaches, partial least squares (PLS) and principal component regression (PCR+) methods were used in data processing. Similar results were obtained with both chemometric methods.     

FT-IR spectrophotometric analysis of dehydroepiandrosterone and its pharmaceutical formulation

A Fourier transform infrared (FT-IR) spectrometric method was developed for the rapid, direct measurement of dehydropeiandrosterone. Conventional KBr spectra and KBr + 2.0 mg microcrystalline cellulose (MCC) spectra were compared for best determination of active substance in drug formulation. Two chemometric approaches, partial least-squares (PLS) and principal component regression (PCR+) methods were used in data processing. The best results were obtained with PCR+ method.     

Determination of celecoxib in pharmaceutical formulations using UV spectrophotometry and liquid chromatography

A new UV spectrophotometric method (UV method) and a reversed phase liquid chromatographic method (LC method) for the quantitative estimation of celecoxib, a selective COX-2 inhibitor, in pure form and in solid dosage form were developed in the present study. The linear regression equations obtained by least square regression method, were Abs=4.949 x 10(-2).Conc. (in microg/ml)+1.110 x 10(-2) for the UV method and Area under the curve=5.340 x 10(1).Conc. (in ng/ml)+3.144 x 10(2) for the LC method, respectively. The detection limit, as per the error propagation theory, was found to be 0.26 microg/ml and 25 ng/ml, respectively, for the UV and LC methods. The developed methods were employed with a high degree of precision and accuracy for the estimation of total drug content in three commercial capsule formulations of celecoxib. The results of analysis were treated statistically, as per International Conference on Harmonisation (ICH) guidelines for validation of analytical procedures, and by recovery studies. The results were found to be accurate, reproducible and free from interference and better than the earlier reported methods.     

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.     

近红外漫反射光谱法测定头孢氨苄胶囊的含量

目的:应用近红外漫反射技术和化学计量学的方法对头孢氨苄胶囊进行定量分析.方法:通过偏最小二乘法建立数学模型,对预测集进行预测,并对实际样品的含量进行分析测定.结果:25个样品经内部交叉验证建立预测模型,内部交叉验证的均方差为0.40,确定系数R2=1.00.用15个样品进行外部验证,外部验证的均方差为0.59,确定系数R2=0.999.预测值与真值的确定系数为0.9995.预测值的平均回收率为100.4%(RSD为0.50%,n=15).方法精密度RSD为0.85%(n=7).结论:建立的预测模型对头孢氨苄胶囊进行含量测定是可行和有效的,样品不需预处理,分析快速、简便、环保,结果准确.     

Data fusion of Fourier transform infrared spectra and powder X-ray diffraction patterns for pharmaceutical mixtures

Fusing complex data from two disparate sources has been demonstrated to improve the accuracy in quantifying active ingredients in mixtures of pharmaceutical powders. A four-component simplex-centroid design was used to prepare blended powder mixtures of acetaminophen, caffeine, aspirin and ibuprofen. The blends were analyzed by Fourier transform infra-red spectroscopy (FTIR) and powder X-ray diffraction (PXRD). The FTIR and PXRD data were preprocessed and combined using two different data fusion methods: fusion of preprocessed data (FPD) and fusion of principal component scores (FPCS). A partial least square (PLS) model built on the FPD did not improve the root mean square error of prediction. However, a PLS model built on the FPCS yielded better accuracy prediction than PLS models built on individual FTIR and PXRD data sets. The improvement in prediction accuracy of the FPCS may be attributed to the removal of noise and data reduction associated with using PCA as a preprocessing tool. The present approach demonstrates the usefulness of data fusion for the information management of large data sets from disparate sources.     

Determination of vitamin B6 in pharmaceutical formulations by flow injection-solid phase spectrophotometry

In this work, a new solid phase spectrophotometric method in association with flow injection analysis for Vitamin B6 (pyridoxine) determination has been developed with direct measurement of light-absorption in C18 material. In the developed method, successive passage of the complex, previously formed in the flowing stream, and eluent through the flow cell and continuous monitoring of the process provided the analytical information needed to determine pyridoxine. Pharmaceutical samples containing Vitamin B6 were previously dissolved in 0.1 mol l(-1) phosphate buffer solution (pH 7.5) and a sample volume of 235 microl was injected directly into carrier stream consisting of a mixture of methanol and 0.1 mol l(-1) phosphate buffer solution adjusted to pH 7.0 (1+1, v/v). The blue indophenol dye produced from the reaction between pyridoxine and N,N-diethyl-p-phenylenediamine after oxidation by potassium hexacyanoferrate(III) was quantitatively retained on C18 support and the spectrophotometric detection was performed simultaneously at 633 nm. The retained complex was quickly eluted from C18 material with the eluent stream consisting of a mixture of methanol and 0.01 mol l(-1) HCl (6+4, v/v). The results showed that the proposed method is simple, rapid and the analytical response is linear in the concentration range of 0.5-10 and 0.2-4 mg l(-1) using 235 and 860 microl of sample, respectively. The limits of detection are 0.15 and 0.060 mg l(-1) and the R.S.D. are 3.6% (at 2 mg l(-1) level) and 4.0% (at 1 mg l(-1) level) using sample volume of 235 and 860 microl, respectively. The system presented an analytical throughput of 15 determinations per hour when a sample volume of 235 microl was utilized. The procedure was successfully applied to the determination of Vitamin B6 in pharmaceutical formulations containing vitamins of B group and others active principles such as Vitamin C and minerals.     

Determination of cisapride in pharmaceutical preparations using derivative spectrophotometry

Derivative spectrophotometric and high performance liquid chromatographic methods (HPLC) were described for the determination of cisapride in pharmaceutical preparations. Spectrophotometrically, cisapride was determined by measuring the 1D-values at 264, 300 nm and 2D-values at 276, 290 and 276-290 nm. Beer's Law was obeyed in the range 2-12 microg ml(-1). The HPLC method depends upon using micropack-Si-10 column at ambient temperature with a mobile phase consisting of methanol-concentrated ammonia (99.25:0.75) at a flow rate of 1 ml min(-1). Quantitation was achieved by UV detection at 272 nm using quinine as internal standard. Calibration curve was linear over the concentration range 2-10 microg ml(-1). Both derivative spectrophotometry and HPLC methods showed good linearity, precision and reproducibility. No interference was found from tablet or suspension matrices at the selected derivative wavelengths and chromatographic conditions. The proposed methods were successfully applied to the assay of commercial tablets and suspension. The procedures were rapid, simple and suitable for quality control applications.     

近红外漫反射光谱法测定阿奇霉素分散片的含量

目的应用近红外漫反射技术和化学计量学的方法对阿奇霉素分散片进行定量分析。方法通过偏最小二乘法建立数学模型,对预测集进行预测,并对实际样品的含量进行测定。结果40个样品经内部交叉验证建立预测模型,内部交叉验证确定系数R2=99.86,内部交叉验证的均方差RM SECV=0.504。用8个样品进行外部验证,预测值与真实值的相关系数达0.9994。预测值的平均回收率为100.2%(RSD=0.85%,n=8),方法精密度RSD=0.89%(n=7),方法稳定性RSD=0.90%(n=7)。结论本方法快速简便,结果准确,适用于对模型涉及企业的药品进行快速检查或质量控制。     

Nuclear medicine techniques in the evaluation of pharmaceutical formulations

Nuclear medicine imaging techniques have great potential in the study of the behaviour of drug formulations and drug delivery systems in human subjects. No other technique can locate so precisely the site of disintegration of a tablet in the Gl tract, the depth of penetration of a nebulised solution into the lung, or the residence time of a drug on the cornea. Using the gamma camera to image the in vivo distribution of pharmaceutical formulations radiolabelled with a suitable gamma emitting radionuclide, images may be used to quantify the biodistribution, release and kinetics of drug formulations and delivery from novel carrier systems and devices. Radionuclide tracer techniques allow correlation between the observed pharmacological effects and the precise site of delivery. The strength of the technique lies in the quantitative nature of radionuclide images. Such studies not only provide data on the nature and characteristics of a product, such as reliability and reproducibility but, may also be used in submission to Regulatory Authorities in product registration dossiers.     

Determination of propylene carbonate in pharmaceutical formulations using liquid chromatography

A stability-indicating reversed-phase high-performance liquid chromatographic method using a refractive index detector is described for the determination of propylene carbonate in pharmaceutical formulations. Good precision and accuracy of the method was demonstrated using an aqueous formulation. This method is also applicable to an anhydrous formulation.     

Determination of tetrahydrozoline hydrochloride and fluorometholone in pharmaceutical formulations by HPLC and derivative UV spectrophotometry

Two methods for the quantitative determination of tetrahydrozoline hydrochloride (1) and fluorometholone (2) in pharmaceutical eye drops (Efemoline) are described. The procedures are based on derivative UV spectrophotometry and HPLC. In the former method, d2A/d lambda 2 values were measured in methanol at 226 and 282 nm for 1 and 2, respectively. The relative standard deviations for the method were found to be 1.06% for 1 and 0.98% for 2. The latter method based on a reversed phase HPLC system using a Partisil 5 ODS analytical column. The mobile phase used for the separation of 1, 2 and internal standard (lidocaine) was methanol/acetonitrile/water (50:50:10 v/v) and the compounds in the eye drops were detected at 220 nm using an UV detector. The relative standard deviations for the HPLC method were determined to be 0.61% and 0.50% for 1 and 2, respectively. The proposed methods, which give thoroughly comparable data, are simple, rapid, and allow precise and accurate results and could be used for commercial formulations containing tetrahydrozoline hydrochloride and fluorometholone in combination.     

Determination of lamivudine and stavudine in pharmaceutical preparations using chemometrics-assisted spectrophotometry

A simple chemometrics-assisted spectrophotometric method for the simultaneous determination of lamivudine and stavudine in pharmaceutical tablets is described. The UV absorption spectra of the studied drugs, in the range of 200–310 nm, showed a considerable degree of spectral overlapping ([D_i]^0.5 = 94.9%). Resolution of the mixture has been accomplished by using classical least-squares regression analysis (CLS) and principle components regression analysis methods (PCR). Beer’s law was obeyed for both drugs in the general concentration ranges of 2–12 and 3–15 μg ml⁻¹ for lamivudine and stavudine, respectively. The proposed methods were successfully applied for the determination of the two drugs in laboratory prepared mixtures. The overall recoveries percent were found 98.58 ± 1.53–101.30 ± 1.35 (CLS) and 98.62 ± 1.65–101.13 ± 1.04 (PCR) for lamivudine and 98.43 ± 1.62–99.42 ± 1.55 (CLS) and 98.23 ± 1.97–101.20 ± 1.79 (PCR) for stavudine, respectively. The commercial tablets percentage content was found 98.10 ± 2.5–102.47 ± 2.94 (CLS) and 99.12 ± 1.71–100.92 ± 1.54 (PCR) for lamivudine and 96.00 ± 2.94–98.17 ± 1.72 (CLS) and 97.40 ± 1.55–97.80 ± 1.92 (PCR) for stavudine, respectively. Good percentage recoveries and proper statistical data obtained with both the laboratory prepared mixtures and the commercial tablets proved the suitability and efficiency of the proposed procedures for routine analysis and quality control purposes with quite satisfactory precision. A comparison of the obtained results from CLS and PCR were also performed with those obtained from reported method. The obtained F- and t-values obtained indicating no significant differences between the results of the proposed and reported methods.     

地奥司明对雄性大鼠良性前列腺增生的改善作用

目的探讨地奥司明对大鼠良性前列腺增生的改善作用及其作用机制。方法 Wistar大鼠随机分为对照组、模型组、地奥司明80、160 mg/kg组,每组各6只。采用手术去势和每日sc 10 mg/kg的丙酸睾酮注射液建立大鼠良性前列腺增生模型,地奥司明组每日ig 80、160 mg/kg地奥司明,各组大鼠连续给药4周。实验结束后分离前列腺组织,观察药物对良性前列腺增生大鼠前列腺指数(PI)、PACP酶活力、前列腺组织形态学变化和前列腺组织氧化应激水平的影响,并采用Western blotting法评价I型胶原(Col-I)、雄激素受体(AR)和雌激素受体-α/β(ER-α/β)表达。结果与模型组比较,地奥司明能够显著降低PI(P0.01),抑制PACP的酶活力(P0.05、0.01)。与模型组比较,地奥司明在一定程度抑制了前列腺上皮增生和胶原沉积。与模型组比较,地奥司明组(160、80 mg/kg)均能显著提升超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)和过氧化氢酶(CAT)的酶活力(P0.05、0.01)。与模型组比较,地奥司明干预可有效升高前列腺还原型谷胱甘肽(GSH)、总巯基(T-SH)水平,降低丙二醛(MDA)、氧化型谷胱甘肽(GSSG)水平(P0.05、0.01)。与模型组比较,地奥司明组Col-I的表达明显降低(P0.01、0.05),160mg/kg地奥司明能显著抑制AR和ER-α的表达(P0.01),80mg/kg地奥司明则明显降低AR的表达(P0.05);且地奥司明能显著提高ER-β的表达(P0.01)。结论地奥司明改善大鼠良性前列腺增生的作用机制与调控前列腺AR、ER-α/β表达和氧化应激有关。     

Determination of meglumine in pharmaceutical formulations using high performance liquid chromatography

Four different approaches were followed for the development of a HPLC method for the determination of meglumine in solid dosage formulations: derivatization of meglumine prior to HPLC analysis, the use of an ion-pairing reagent in the mobile phase, the use of charged surface hybrid stationary phase and the use of a column designed for carbohydrate separations. The method using anionic pairing reagent in the mobile phase was shown to be suitable for the quantitative determination of meglumine in solid dosage forms. The HPLC separation was achieved on an Agilent Eclipse XDB-C18 column (150 mm x 4.6 mm, 3.5 microm particle size) using a mobile phase with octane-1-sulfonic acid. The method was validated and validation included the following studies: selectivity, precision (repeatability), linearity and accuracy. During validation experiments RID and DAD detectors were used.     

Determination of lignocaine and amprolium in pharmaceutical formulations using AAS.

The ion-associate complexes of lignocaine hydrochloride (Lig.Cl) with ammonium reineckate (Rk) or sodium cobaltithiocyanate, and that of amprolium hydrochloride (Amp.Cl) with ammonium reineckate, have been prepared. The precipitated ion-associates were subjected to elemental analyses, infrared and nuclear magnetic resonance spectroscopy and determination of the metal content for elucidation of their structures. The solubilities of the solid ion-associate complexes have been studied and their solubility products were determined at different temperatures at the optimum pH for their quantitative precipitation. The thermodynamic parameters DeltaH, DeltaG and DeltaS for the dissolution of the ion-associate complexes were calculated. These ion-associate complexes have been used for the quantitative determination of the above mentioned drugs by precipitating them with an excess of the inorganic metal complex ions and determining the excess metal complex ions using atomic absorption spectrometry. The method was applied for the determination of the above drugs in pure solution and pharmaceutical preparations. 0.135-135.4 and 0.158-157.6 mg of lignocaine and amprolium, respectively, can be determined with mean relative standard deviations (R.S.D.) 0.92-1.20% and recovery values of 99.18+/-0.48 to 100.12+/-0.34% indicating high precision and accuracy.     

Determination of bile acids in pharmaceutical formulations using micellar electrokinetic chromatography

A micellar electrokinetic chromatography method (MEKC) has been developed and validated for the determination of bile acids (BA) such as ursodeoxycholic acid (UDCA), dehydrocholic acid (DHCA) and deoxycholic acid (DCA) in pharmaceuticals for quality control purpose. The background electrolyte consisted of 20 mM borate-phosphate buffer containing 50 mM sodium dodecylsulfate (SDS), and acetonitrile as additive. UV detection was set at 185 nm. Selectivity, linearity, range, repeatability, intermediate precision and accuracy showed good results. Comparison of the values obtained by MEKC and HPLC methods were in close agreement.     

Determination of simvastatin-induced changes in bone composition and structure by Fourier transform infrared spectroscopy in rat animal model

Simvastatin is a hypolipidemic drug which is used to control hypercholesterolemia and to prevent cardiovascular disease. In the current study, the effects of high and low doses of simvastatin treatment on tibia of healthy rats were investigated. Wistar rats were used for the control, 20 mg and 50 mg simvastatin-treated groups. Molecular investigations were performed using Fourier transform infrared spectroscopy. In the bones of the two groups of simvastatin-treated rats, the relative mineral/matrix ratio (p < 0.001), relative carbonate content (p < 0.001), carbonate/amide I ratio (p < 0.001) and crystallinity (p < 0.001) decreased significantly compared to the control group. Low dose of simvastatin treatment is more effective in reducing the relative carbonate content indicating the amount of carbonate substitution for phosphate in the mineral crystal. The olefinic band almost disappeared in the high dose of simvastatin-treated group which implies a decrease in unsaturation and an increase in lipid peroxidation. The higher frequency value and the bandwidth of CH₂ asymmetric stretching band for the 50 mg treated group imply more disordered (p < 0.001) and fluid (p < 0.001) membrane structure. Low dose of simvastatin is more effective in strengthening the bone than high dose simvastatin treatment. High dose simvastatin treatment induces lipid peroxidation and changes the lipid composition and concentration, which are known to affect membrane physical properties.     

地奥司明联合物理治疗对腰椎间盘突出症的疗效分析

目的 探讨地奥司明联合红外线理疗治疗腰椎间盘突出症的疗效.方法 选择本院2011年1月～2012年12月收治的腰椎间盘突出症患者160例,随机分为对照组和治疗组各80例,对照组患者口服地奥司明片,治疗组患者在此基础上给予红外线物理治疗;疗程结束后比较两组患者临床疗效和JOA评分情况.结果 治疗组总有效率达81.2％,明显优于对照组,差异有统计学意义（x2=6.957,P＜0.05）;两组患者治疗后JOA评分均有所升高,其中治疗组升高更明显,两组差异有统计学意义（P＜0.01）.结论 地奥司明联合红外线物理治疗可明显减缓腰椎间盘突出症患者的腰腿疼痛,疗效显著,值得临床推广.