Chemometric and derivative methods as flexible spectrophotometric approaches for dissolution and assaying tests in multicomponent tablets

Two derivative spectrophotometric (ratio derivative spectra and algorithm bivariate calibration) and a chemometric methods (partial least squares, PLS) are proposed for the simultaneous determination of binary mixtures in tablet analysis and dissolutions tests, without prior separation. These approaches are successfully applied to quantify trimethoprim (TMP) combined with sulfamethoxazole (SMX) or sulfamethazine (SMZ) or sulfafurazole (SFZ) using the information in the absorption spectra of appropriate solutions. Beer's law was obeyed in the concentration range of 0.98-17.5 microg/ml for TMP, 0.95-17.2 microg/ml for SMX, 1.16-17.5 microg/ml for SMZ and 0.97-17.4 microg/ml for SFZ. The first derivative (1D) bivariate algorithm method involves the use of four calibration curves: two for each compound at two different wavelengths, selected by Kaiser's method. Similarly, the first derivative ratio spectrophotometry employs the linear relationship between the ratio spectra of the analytes and the concentration range. The results were compared with those obtained by PLS multivariate calibration. The calibration models from PLS were pre-treated by orthogonal signal correction and evaluated by cross-validation using the 'SIMCA-P 9' software. Synthetic mixtures of TMP and sulfonamides were used in five different sets for the validity of the calibrations. Mean recoveries for derivative ratio, derivative bivariate and PLS methods were found to be between 99.7% and 102.0% for TMP, 99.4% and 100.2% for SMX, 99.3% and 101.0% for SMZ and 98.1% and 102.3% for SFZ. The calibrations of the three methods were successfully applied to the assaying and dissolution of placebo and commercial tablets without any prior separation. More than 85% of TMP, SMX and SMZ were dissolved within 15 min. For SFZ, only 85% of the compound was dissolved after 60 min. In this study, the three spectrophotometric methods can be satisfactorily used for the quantitative analysis and for dissolution tests of multicomponent dosage forms.     

反相高效液相色谱法和二阶导数分光光度法两种测定维生素E乳膏含量方法的比较

目的：对维生素E乳膏两种含量测定方法的比较。方法：按照分析方法验证指导原则相关要求对反相高效液相色谱法和二阶导数分光光度法测定维生素E乳膏含量进行比较。结论：在回收率,重复性,中间精密度上两种方法均较好,差异也不明显。耐用性方面,二阶导数分光光度法相关因素影响较小。     

A study of derivative spectrophotometry for the determination of carboxyhemoglobin in blood

An application of derivative spectrophotometry to the determination of carboxyhemoglobin (HbCO) in blood was examined. The 1st, 2nd, 3rd, and 4th derivative spectra were recorded in the Soret region for HbCO, reduced hemoglobin (Hb), and their mixed solution. The 4th derivative spectrum had the highest sensitivity to the change of HbCO-Hb ratio in the solution. A maximum point of the 4th derivative curve was employed for the HbCO determination. Blood samples with varied HbCO concentrations were analyzed using this technique and the results were compared with those obtained by conventional spectrophotometric and gas chromatographic procedures. The derivative method was in satisfactory agreement with both procedures.     

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.     

Determination of nimesulide in pharmaceutical dosage forms by second order derivative UV spectrophotometry

In this study, nimesulide which has been used as an analgesic, antipyretic and anti-inflammatory agent, was analyzed by using second order derivative UV spectrophotometry. The solvent, the degree of derivation, ranges of wavelength and n-value were chosen in order to optimize the conditions. The concentration of nimesulide in its solutions in ethanol and chloroform were determined between the wavelength ranges of 200 and 500 nm (n = 6, delta lambda = 21) and in the linearity ranges of 2.0-90.0 microg ml(-1) in ethanol and 2.0-50.0 microg ml(-1) in chloroform by using the values obtained from the second derivative UV spectrum of the substance. The developed second derivative UV spectrophotometric method was applied to the pharmaceutical preparations such as tablet, sachet (granule) and suspension. Tablet and sachet were analysed in ethanol while the suspension was analysed in chloroform. The results obtained from derivative UV spectrophotometry were compared with those obtained by using HPLC. It was found that the difference was not statistically important between these methods. It was concluded that developed derivative UV spectrophotometric method was accurate, sensitive, precise, reproducible and could be applied directly and easily to the pharmaceutical preparations.     

Spectrophotometric determination of indinavir in bulk and pharmaceutical formulations using bromocresol purple and bromothymol blue

A simple, sensitive and selective method for the determination of indinavir (IND) in bulk and in pharmaceutical formulations is described. The method is based on extraction of this drug into chloroform as ion-pair with sulphonphthalein dyes as bromocresol purple (BCP) and bromothymol blue (BTB). The optimum conditions of the reactions were studied and optimized. The absorbance of the yellow products was measured at 427 nm for IND-BCP and 420 nm for IND-BTB. The calibration graphs were linear over the range 4.0-60.2 microg x ml(-1) of drug in chloroform, using the two dyes. The composition of the ion-pairs was established by the molar ratio method. For IND the molar ratio was determined to be 1:1 by measurement of first derivative signals at 273 nm. A calibration graph was established for 3.0-70.6 microg x ml(-1) of IND for first derivative spectrophotometry. The developed method was applied successfully for the determination of IND in pharmaceutical formulations. The data obtained were compared the data given by first derivative spectrophotometry. No differences were found.     

Determination of astemizole in pharmaceutical preparations using spectrophotometric methods

UV absorption and second derivative spectrophotometric methods were developed for the determination of astemizole in commercial pharmaceutical formulations containing this compound alone. Solutions of astemizole in 0.1 M HCl:methanol (1:3) were used in the methods and the linearity range was 4.6-45.8 microg ml(-1) in both methods. The mean recoveries and relative standard deviations were calculated and the method was applied to two commercial preparations marketed in Turkey. Results were compared with the literature method, HPLC. Also, two new spectrophotometric methods are described for the simultaneous determination of astemizole and pseudoephedrine hydrochloride in their combination. In the first method, first derivative spectrophotometry, dA/dlambda values were read at selected wavelengths in zero-crossing points in the first derivative spectra of the mixture solution in 0.1 M HCl:methanol (1:3). In the second, ratio spectra derivative spectrophotometry, analytical signals were measured at the wavelengths corresponding to either maximums and minimums for both drugs in their solution in 0.1 M HCl:methanol (1:3) in the first derivative spectra of their ratio spectra. The procedures do not require any separation step. The mean recoveries were found satisfactory in the methods.     

Spectrophotometric resolution of metronidazole and miconazole nitrate in ovules using ratio spectra derivative spectrophotometry and RP-LC

Metronidazole and miconazole nitrate in ovules was determined by ratio spectra derivative spectrophotometry and by high-performance liquid chromatography (HPLC). The first method depends on ratio spectra first derivative spectrophotometry, by utilizing the linear relationship between substances concentration and ratio spectra first derivative peak amplitude. The ratio first derivative amplitudes at 242.6 [(1)DD(242.6)], 274.2 [(1)DD(274.2))] 261.8 [(1)DD(261.8))] 273.5 [(1)DD(273.5))]and 281.5 [(1)DD(281.5)] nm were selected for the assay of metronidazole and miconazole nitrate, respectively. The second method is based on high-performance liquid chromatography on a reversed-phase column using a mobile phase of methanol-water-phosphoric acid (30:70:0.20 v/v) (pH 2.8) with programmable detection at 220.0 nm. The minimum concentration detectable by HPLC was 0.9 microg ml(-1) for metronidazole and 0.3 microg ml(-1) for miconazole nitrate and by ratio derivative spectrophotometry 4.0 microg ml(-1) for metronidazole and 0.5 microg ml(-1) for miconazole nitrate. The proposed procedures were successfully applied to the simultaneous determination of metronidazole and miconazole nitrate in ovules with a high percentage of recovery, good accuracy and precision.     

小波变换-比值导数光谱法同时测定脑清片中氨基比林和咖啡因的含量

目的　建立小波变换-比值导数光谱法（WT-RDS）,考察其在多组分样品含量测定中去除高频噪音干扰的作用。方法　采用WT-RDS同时测定脑清片中氨基比林和咖啡因的含量,以两组分样品的原始光谱除以其中某一组分的标准光谱后得到比值光谱,再以比值光谱对波长求导得到比值导数光谱。选取适当波长的振幅值测定,可消除一个组分的干扰而测定另一组分的含量;比较各实验数据小波变换前后处理的结果。结果　采用小波变换技术可消除测定组分的比值导数光谱中被“放大”的噪音的影响,实验数据的线性关系、精密度等得到改善。结论　WT-RDS灵敏度高,抗干扰能力强,结果可靠。     

非相关成分参比一倍率导数光谱法测定制剂中甲氧苄啶和磺胺甲(口恶)唑

提出了非相关成分参比一倍率导数光谱法用于测定混合组分体系的基本原理和实验方法。本法可用于待测成分和非相关成分导数光谱严重重叠且待测成分含量较低时的不经分离直接测定。试用本法消除了甲氧苄啶(TMP)和磺胺甲嚼唑(SMZ)及附加剂之间的相互干扰,从而测定了部分制剂中的TMP:用“零交法”测定了SMZ,平均回收率分别为:102.5±1.63%(CV)和100.3±0.99%(CV)。     

Determination of serum acetaminophen in emergency toxicology: evaluation of newer methods: Abbott TDx and second derivative ultraviolet spectrophotometry

Newer methods for the determination of serum acetaminophen in emergency toxicology, the Abbott TDx immunoassay and second derivative ultraviolet spectrophotometry, were evaluated and compared to a high pressure liquid chromatographic procedure. The Abbott TDx immunoassay within-run and day to day precision yielded coefficients of variance below 2.7% and 7.2% respectively: Abbott TDx immunoassay results correlated well with those of high pressure liquid chromatographic in patient serums 15.0 to 333 mg/L acetaminophen; r2 = 0.954, n = 40. The Abbott TDx immunoassay assay was rapid, easy to perform, free of interferences from other drugs and exhibited no carryover from previous samples. The within run precision of the second derivative ultraviolet spectrophotometry method yielded coefficients of variance of less than 7.0%. Second derivative ultraviolet spectrophotometry results demonstrated good correlation with high pressure liquid chromatographic results in patient sera; r2 = 0.923, n = 40; however, performance deteriorated below 50.0 mg/L acetaminophen. Spectral interferences were noted at high concentrations of some drugs.     

Determination of Amiodarone Hydrochloride in Pharmaceutical Formulations by Derivative UV Spectrophotometry and High-Performance Liquid Chromatography (HPLC)

Assay procedures based on derivative ultraviolet spectrophotometry and high-performance liquid chromatography (HPLC) have been developed for the specific determination of amiodarone hydrochloride in pharmaceutical dosage forms. The use of first- and second-order derivative spectrophotometry was found to have suppressed the background absorption from the excipients with comparable accuracy and precision to the reversed-phased HPLC reference method. A conventional UV absorption method ( = 242 nm) is subject to possible interference by formulation excipients.     

紫外及零交导数先谱法测定输液中茶碱和西咪替丁的含量

紫外及零交导数先谱法测定输液中茶碱和西咪替丁的含量陈鸣（新疆医学院二附院药剂科，乌鲁木齐８３００２８）ＴｈｅＤｅｔｅｒｍｉｎａｔｉｏｎｏｆＴｈｅｏｐｈｙｌｌｉｎｅａｎｄＣｉｍｅｔｉｄｉｎｅｉｎＦｌｕｉｄＩｎｆｕｓｉｏｎｂｙＵＶａｎｄＺｅｒｏ－ｃｒｏｓ...     

Simultaneous determination of dorzolamide HCL and timolol maleate in eye drops by two different spectroscopic methods

Two-component mixtures of dorzolamide hydrochloride and timolol maleate were assayed by first derivative and ratio derivative spectrophotometric methods. The first method, derivative spectrophotometry, by the zero-crossing measurements, was used due to the drugs closely overlapping absorption spectra. Linear calibration graphs of first derivative values at 250.3 nm for dorzolamide hydrochloride and 315.8 nm for timolol maleate. The second method, is based on ratio first derivative spectrophotometry, the amplitudes in the first derivative of the ratio spectra at 242.9 and at 223.5 nm were selected to determine dorzolamide and timolol maleate in the binary mixture. Calibration graphs were established for 8.0-30.0 microg ml(-1) for dorzolamide hydrochloride and 3.0-24.6 microg ml(-1) for timolol maleate in binary mixture. Good linearity, precision and selectivity were found, and the proposed methods were applied successfully to the pharmaceutical dosage from containing the above-mentioned drug combination without any interference by the excipients. Vierordt's method was also developed for a comparison method.     

二阶导数光谱法同时测定双组分体系中阿司匹林和水杨酸的含量

目的：建立二阶导数紫外光谱法同时测定双组分体系中阿司匹林和水杨酸浓度。方法：配制阿司匹林和水杨酸的系列标准溶液,记录样品在230～350nm的紫外扫描图谱,并求二阶导数光谱;采用二阶导数光谱法和等吸收波长法分别测定混合物中阿司匹林和水杨酸的含量,计算回收率。结果：二阶导数光谱法测定双组分体系中阿司匹林的平均回收率为（100.32±0.94）%,水杨酸的平均回收率为（100.34±0.61）%;等吸收波长法能够准确测定混合体系中阿司匹林的含量,测定回收率为（99.66±1.17）%,但水杨酸测定误差较大,平均回收率为（104.16±3.65）%。结论：二阶导数光谱法操作简便,结果准确,可同时准确测定双组分体系中阿司匹林和水杨酸的含量。     

二阶导数光谱法测定复方异丙嗪糖浆中盐酸异丙嗪的含量

目的用紫外分光光度法不经分离直接测定复方异丙嗪糖浆中盐酸异丙嗪的含量。方法二阶导数光谱法,测定波长为256nm。结果盐酸异丙嗪在5．21～31．26ug/ml浓度范围内线性关系良好,峰零间振幅D对浓度C的回归方程C=-651．25×D＋0．3256,r=1．0000,平均回收率为101．10％,相对标准偏差为0．98％。结论二阶导数光谱法测定复方异丙嗪糖浆中盐酸异丙嗪含量简便、快速、结果准确。     

Determination of binary mixtures of analgesic and spasmolytic drugs in pure and dosage forms by derivative spectrophotometry

Binary mixtures of dipyrone and pitophenone hydrochloride are assayed by zero-crossing second- and third-derivative spectrophotometry and by ratio-spectra first- and second-derivative spectrophotometry. In the first method, calibration plots are linear at 266.5 and 302.5 nm (dipyrone, second derivative), and 257 and 286 nm (pitophenone second derivative) and 242 and 278.3 nm (dipyrone third derivative), and 228.5 and 300 nm (pitophenone, third-derivative). By the second method, lines of regression are linear at 235 and 262 nm (dipyrone, first derivative), and 229.5 and 288.5 nm (pitophenone, first-derivative), and 249.7 and 268 nm (dipyrone, second derivative), and 280.5 and 300 nm (pitophenone, second-derivative). In all methods calibration curves follow the Beer's law up to 40 microg/ml of each drug. LOD and LOQ values were calculated. The developed derivative spectrophotometric methods were applied to laboratory mixtures and to vials for these drugs. The procedures are simple, rapid, and did not require any preliminary separation or treatment of the samples.     

Simultaneous determination of hydrochlorothiazide and amiloride hydrochloride by ratio spectra derivative spectrophotometry and high-performance liquid chromatography

Rapid, precise, accurate and specific ratio spectra derivative spectrophotometry and high-performance liquid chromatographic procedures were described for the simultaneous determination of hydrochlorothiazide and amiloride hydrochloride in combined pharmaceutical dosage forms. For the first method, ratio spectra derivative spectrophotometry, the signals were measured at 285.7 nm for hydrochlorothiazide and at 302.5 nm for amiloride hydrochloride in the mixture, in the first derivative of the ratio spectra. The second method is based on high-performance liquid chromatography (HPLC) on LiChrosorb RP-C18 column (5 microm, 20 cm x 4.6 mm) using 0.025 M orthophosphoric acid (adjusted to pH 3.0 with triethylamine (TEA)), acetonitrile (84:16 v/v) as a mobile phase at a flow rate of 1.2 ml/min(-1). Detection was carried out using a UV detector at 278.0 nm. Commercial sugar-coated and laboratory-prepared mixtures containing both drugs in different proportions were assayed using the developed methods.     

Rapid and simple methods for quantitative analysis of some antidepressant in pharmaceutical formulations by using first derivative spectrophotometry and HPLC

Two rapid, simple and accurate first derivative spectrophotometry and HPLC method for the determination of nefazodone hydrochloride and sertraline hydrochloride in pharmaceutical formulations are discussed. The first one is a derivative spectrophotometric procedure and the second one is based on a HPLC method with a UV detector. In the first method, first derivative spectrophotometry, nefazodone hydrochloride or sertraline hydrochloride by measurement of their first derivative signals at 241.8-256.7 nm (peak-to-peak amplitude), or 271.6-275.5 nm (peak-to-peak amplitude), respectively. Calibration graphs were established for 10.0-42.0 microg ml(-1) nefazodone hydrochloride, or 8.0-46.0 microg ml(-1) sertraline hydrochloride. In the other method, HPLC, the UV detection was carried out at 265.0 nm (nefazodone hydrochloride) and 270.0 nm (sertraline hydrochloride). The samples were chromatographed on a Supercosil RP-18 column. The mobile phases were methanol:acetonitrile:phosphate buffer at pH 5.5 (10:50:40 v/v/v) (nefazodone hydrochloride) and methanol:phosphate buffer at pH 4.5 (20:80 v/v) (sertraline hydrochloride). The results obtained from first derivative spectrophotometric method were comparable with those obtained by using HPLC. It was concluded that both the developed methods are equally accurate, sensitive, and precision could be applied directly and easily to the pharmaceutical formulations of nefazodone hydrochloride and sertraline hydrochloride, respectively.     

First order derivative spectrophotometric and HPLC methods for determination of moexipril hydrochloride in the pure form, pharmeceutical formulations and evaluation of its stability

A rapid, linear (over a concentration range of 0.00012-0.0012% and with correlation coefficient r = 0.999), accurate (an average recovery of 100%), precise (an average standard deviation < 1.5%) and economical first derivative UV spectrophotometric assay method (lambda(max) = 238 nm) was developed for the determination of moexipril hydrochloride (MOXL) in a pharmaceutical formulation. The method was investigated for its utility for the determination of MOXL in commercially available tablets and as a stability-indicative assay in solid state. The results obtained by means of the investigated method were statistically compared (t-Student test and F-Snedecor test) with the results obtained by means of the reference method--HPLC, which evidenced that both methods are equally precise and accurate. It was finally concluded that first derivative UV spectrophotometry is selective with reference to excipients used for the tablets' formulation, however, it is not selective with reference to MOXL degradation products.