Simultaneous determination of three fluoroquinolones by linear sweep stripping voltammetry with the aid of chemometrics

A linear sweep stripping voltammetric (LSSV) method has been researched and developed for simultaneous quantitative determination of mixtures of three antibiotic drugs, ofloxacin, norfloxacin and ciprofloxacin. It relies on reductive reaction of the antibiotics at a mercury electrode in a Britton-Robinson buffer (pH 3.78). The voltammograms of these three compounds overlap strongly, and show non-linear character. Thus, it is difficult to analyse the compounds individually in their mixtures. In this work, chemometrics methods such as classical least squares (CLS), principal component regression (PCR), partial least squares (PLS) and radial basis function-artificial neural networks (RBF-ANN) were applied for the simultaneous determination of these compounds. The prediction performance of the calibration models constructed on the basis of these methods was compared. It was shown that satisfactory quantitative results were obtained with the use of the RBF-ANN calibration model relative prediction error (RPE_T) of 8.1% and an average recovery of 101%. This method is able to accommodate non-linear data quite well. The proposed analytical method based on LSSV was applied for the analysis of ofloxacin, norfloxacin and ciprofloxacin antibiotics in bird feedstuffs and their spiked samples, as well as in eye drops with satisfactory results.     

Simultaneous determination of vitamin B12 and its derivatives using some of multivariate calibration 1 (MVC1) techniques

Resolution of binary mixtures of vitamin B12, methylcobalamin and B12 coenzyme with minimum sample pre-treatment and without analyte separation has been successfully achieved by methods of partial least squares algorithm with one dependent variable (PLS1), orthogonal signal correction/partial least squares (OSC/PLS), principal component regression (PCR) and hybrid linear analysis (HLA). Data of analysis were obtained from UV-vis spectra. The UV-vis spectra of the vitamin B12, methylcobalamin and B12 coenzyme were recorded in the same spectral conditions. The method of central composite design was used in the ranges of 10-80mgL(-1) for vitamin B12 and methylcobalamin and 20-130mgL(-1) for B12 coenzyme. The models refinement procedure and validation were performed by cross-validation. The minimum root mean square error of prediction (RMSEP) was 2.26mgL(-1) for vitamin B12 with PLS1, 1.33mgL(-1) for methylcobalamin with OSC/PLS and 3.24mgL(-1) for B12 coenzyme with HLA techniques. Figures of merit such as selectivity, sensitivity, analytical sensitivity and LOD were determined for three compounds. The procedure was successfully applied to simultaneous determination of three compounds in synthetic mixtures and in a pharmaceutical formulation.     

微分脉冲溶出伏安-偏最小二乘法同时测定代森锌和代森锰

采用循环伏安法讨论了两种常用的杀菌剂代森锰和代森锌在汞电极上的电化学还原反应机理,发现它们均具有良好的的伏安还原峰.采用微分脉冲溶出伏安法研究本体系时,获得的代森锰和代森锌的线性范围分别为0.005～0.07 mg/L和0.02～0.24 mg/L;检出限分别为4.10和12.8μg/L.由于这两种杀菌剂的分子结构很相似,它们的伏安波谱峰重叠严重,采用常规方法很难对它们分别进行测定.为解决波谱重叠的问题,本研究采用主成分回归和偏最小二乘法对波谱进行解析.结果表明,偏最小二乘法能得到较好的定量结果.利用本方法对几种蔬菜和水果样品进行分析,三氯甲烷作萃取剂的萃取率最大,回收率在95.5％～103％之间.     

微分脉冲溶出伏安法结合化学计量学测定醚类除草剂

在pH=6.82的Britton-Robinson缓冲溶液中,采用循环伏安法和微分脉冲溶出伏安法对醚类除草剂甲羧除草醚(Bifenox)和三氟羧草醚(Acifluofen)的伏安行为进行了研究,发现吸附时间为50 s时此电化学体系达到平衡,而且微分脉冲溶出伏安法能给出较高的灵敏度,甲羧除草醚和三氟羧草醚分别在-685 mV和-700 mV处具有良好还原峰,但由于峰电位接近而谱峰重叠,很难分别测定.本文采用化学计量学方法来解析重叠峰并完成这两种除草剂的定量分析.甲羧除草醚和三氟羧草醚的测定线性范围分别为0.02～0.18 μg·5mL~(-1)和0.02～0.16 μg·5mL~(-1),检出限分别为0.0073 μg·5mL~(-1)和0.0068 μg·5mL~(-1).利用该方法对水样中的甲羧除草醚和三氟羧草醚进行直接测定,获得了较好的定量分析结果.     

Simultaneous Determination of Three Synthetic Glucocorticoids by Differential Pulse Stripping Voltammetry with the Aid of Chemometrics

Abstract

A novel voltammetric method for simultaneous determination of the glucocorticoid residues prednisone, prednisolone, and dexamethasone was developed. All three compounds were reduced at a mercury electrode in a Britton–Robinson buffer (pH 3.78), and well-defined voltammetric waves were observed. However, the voltammograms of these three compounds overlapped seriously and showed nonlinear character, and thus, it was difficult to analyze the compounds individually in their mixtures. In this work, two chemometrics methods, principal component regression (PCR) and partial least squares (PLS), were applied to resolve the overlapped voltammograms, and the calibration models were established for simultaneous determination of these compounds. Under the optimum experimental conditions, the limits of detection (LOD) were 5.6, 8.3, and 16.8 µg l^?1 for prednisone, prednisolone, and dexamethasone, respectively. The proposed method was also applied for the determination of these glucocorticoid residues in the rabbit plasma and human urine samples with satisfactory results.     

Simultaneous fluorometric determination of nalidixic acid and 7-hydroxymethylnalidixic acid by partial least squares calibration

The resolution of binary mixtures of nalidixic acid (NA) and 7-hydroxymethylnalidixic acid (OH-NA) has been accomplished by partial least squares (PLS) and principal component regression (PCR) multivariate calibration. The method of determination is based on the fluorescence emission of these compounds in the presence of gamma-cyclodextrin (gamma-CD). The formation of the inclusion compounds gives rise to an increase of the fluorescence emission compared to aqueous solution. The total luminescence information of the compounds has been used to optimize the spectral data set to perform the calibration. A comparison between the predictive ability of three multivariate calibration methods, PLS-1, PLS-2 and PCR, on three spectral data sets, excitation, emission and synchronous spectra has been performed. The PLS-1 method, applied to the emission spectra, has been selected as optimum. The proposed method has been applied to the simultaneous determination of NA and OH-NA in urine. Recovery values from urine samples containing (NA) and (OH-NA) range from 91 to 103% (mean 97%), and from 92 to 105% (mean 99%), respectively.     

Application of multivariate curve resolution alternating least squares (MCR-ALS) to the quantitative analysis of pharmaceutical and agricultural samples

Application of multivariate curve resolution alternating least squares (MCR-ALS), for the resolution and quantification of different analytes in different type of pharmaceutical and agricultural samples is shown. In particular, MCR-ALS is applied first to the UV spectrophotometric quantitative analysis of mixtures of commercial steroid drugs, and second to the near-infrared (NIR) spectrophotometric quantitative analysis of humidity and protein contents in forage cereal samples. Quantitative results obtained by MCR-ALS are compared to those obtained using the well established partial least squares regression (PLSR) multivariate calibration method.     

Simultaneous determination of paracetamol,phenylephrine hydrochloride and chlorpheniramine maleate in pharmaceutical preparations using multivariate calibration 1

Resolution of binary mixtures of paracetamol, phenylephrine hydrochloride and chlorpheniramine maleate with minimum sample pre-treatment and without analyte separation has been successfully achieved by methods of partial least squares algorithm with one dependent variable, principal component regression and hybrid linear analysis. Data of analysis were obtained from UV–vis spectra of the above compounds. The method of central composite design was used in the ranges of 1–15 mg L^?1 for both calibration and validation sets. The models refinement procedure and their validation were performed by cross-validation. Figures of merit such as selectivity, sensitivity, analytical sensitivity and limit of detection were determined for all three compounds. The procedure was successfully applied to simultaneous determination of the above compounds in pharmaceutical tablets.     

混合线性分析-分光光度法同时测定微量锌、镉、汞

提出了以2－（5－溴－2－吡啶偶氮）－5－二乙氨基酚为显色剂分光光度法同时测定锌、镉、汞的新方法。由于在可见区3种络合物的吸收光谱具有相似的特征和严重重叠,本文采用混合线性分析进行光谱分辨,各组分的纯光谱则用最小二乘法从校正集中求出。讨论了显色条件,波长选择,纯光谱的确定和吸光度加合性等因素对测定的影响。方法具有简单,快速,准确等优点。已成功地应用于混合试样中锌、镉、汞的同时测定,并与同条件下偏最小二乘法的计算结果进行了对比。     

Comparative study of net analyte signal-based methods and partial least squares for the simultaneous determination of amoxycillin and clavulanic acid by stopped-flow kinetic analysis

A comparative study about advantages and limitations of net analyte signal (NAS)-based methods (NBMs) and partial least squares (PLS) calibration in kinetic analysis has been performed. The different multivariate calibration methods were applied to the determination of binary mixtures of amoxycillin and clavulanic acid, by stopped-flow kinetic analysis. The reactions of oxidation of these compounds with cerium(IV), in sulphuric acid medium, were monitored by following the changes on the fluorescence of the oxidation products, in stopped-flow mode. The differences on the kinetic profiles obtained at λ_ex=256 nm and λ_em=351 nm, were used to determine mixtures of both compounds by multivariate calibration of the kinetic data, using PLS-1, a modification of hybrid linear analysis (HLA) and net analyte pre-processing combined with classical least squares (NAP/CLS) methods. The NBMs allowed the selection of optimal time data regions by calculating the minimum error indicator function (EIF), improving the results and making NBMs very convenient for the analysis. In addition, the use of the net analyte signal concept allows the calculation of the analytical figures of merit, limit of detection (LOD), sensitivity and selectivity, for each component.     

Resolution of mixtures of three nonsteroidal anti-inflammatory drugs by fluorescence using partial least squares multivariate calibration with previous wavelength selection by Kohonen artificial neural networks

A spectrofluorometric method for the quantitative determination of flufenamic, mefenamic and meclofenamic acids in mixtures has been developed by recording emission fluorescence spectra between 370 and 550 nm with an excitation wavelength of 352 nm. The excitation–emission spectra of these compounds are deeply overlapped which does not allow their direct determination without previous separation. The proposed method applies partial least squares (PLS) multivariate calibration to the resolution of this mixture using a set of wavelengths previously selected by Kohonen artificial neural networks (K-ANN). The linear calibration graphs used to construct the calibration matrix were selected in the ranges from 0.25 to 1.00 μg ml⁻¹ for flufenamic and meclofenamic acids, and from 1.00 to 4.00 μg ml⁻¹ for mefenamic acid. A cross-validation procedure was used to select the number of factors. The selected calibration model has been applied to the determination of these compounds in synthetic mixtures and pharmaceutical formulations.     

通用模拟退火用于稳健多元分析校正

模拟退火是一种全局优化算法，具有跨越局部最优点的机制，最小一乘是一种较常用的最小二乘更为稳健的优化准则，更适用于可能偏离正态分布的实际数据集，本文探讨了用最小一乘为准则并利用模拟退火方法同时测定多组分体系的可能性。应用于2－3组分药物体系分析，获得了满意的结果，本文还探讨了改变步长提高模拟退火算法优化精度的方法。     

主成分分析-紫外光谱法同时测定四种维生素B

采用主成分分析法(PCA)完成对多组分样品分析的建模及解析研究,用于处理紫外光谱数据,实现了维生素B_1、B_2及B_6及烟酰胺四组分的同时测定,结果可靠,操作简便。     

Simultaneous Determination of Mepyramine Maleate,Lidocaine Hydrochloride,and Dexpanthenol in Pharmaceutical Preparations by Partial Least‐Squares Multivariate Calibration

Abstract

A partial least‐squares calibration (PLS) method has been developed for simultaneous quantitative determination of mepyramine maleate (MAM), lidocaine hydrochloride (LIH), and dexpanthenol (DPA) in pharmaceutical preparations. The resolution of these mixtures has been accomplished by using partial least‐squares (PLS‐2) regression analysis of electronic absorption spectral data without prior separation or derivatization. The experimental calibration matrix was constructed with 27 samples. The concentration ranges considered were 2, 3, 4 µg mL^?1 for MAM, 2, 3, 4 µg mL^?1 for LIH, and 8, 10, 12 µg mL^?1 for DPA. The absorbances were recorded between 190 and 340 nm every 5 nm. The results show that PLS‐2 is a simple, rapid, and accurate method applied to the determination of these compounds in pharmaceuticals.     

Multivariate curve resolution of overlapping voltammetric peaks: quantitative analysis of binary and quaternary metal mixtures

The application of multivariate curve resolution-alternating least squares (MCR-ALS) to the quantitative analysis of different metal ion mixtures using voltammetric data is described. The performance of MCR-ALS was evaluated in the resolution and quantitation of overlapped voltammetric peaks obtained in the analysis of binary and quaternary mixtures of Cd(II), In(III), Pb(II) and Tl(I) metal ions by anodic stripping voltammetry. Quality assessment of qualitative and quantitative determinations was evaluated considering the effects of different constraints and of initial estimations. MCR-ALS results were validated and compared with those obtained by applying other well-established multivariate calibration methods, such as partial least squares (PLS) and direct classical least squares (DCLS) methods.     

Simultaneous determination of potassium guaiacolsulfonate, guaifenesin, diphenhydramine HCl and carbetapentane citrate in syrups by using HPLC-DAD coupled with partial least squares multivariate calibration

A simple and rapid analytical procedure was proposed for the determination of chromatographic peaks by means of partial least squares multivariate calibration (PLS) of high-performance liquid chromatography with diode array detection (HPLC-DAD). The method is exemplified with analysis of quaternary mixtures of potassium guaiacolsulfonate (PG), guaifenesin (GU), diphenhydramine HCI (DP) and carbetapentane citrate (CP) in syrup preparations. In this method, the area does not need to be directly measured and predictions are more accurate. Though the chromatographic and spectral peaks of the analytes were heavily overlapped and interferents coeluted with the compounds studied, good recoveries of analytes could be obtained with HPLC-DAD coupled with PLS calibration. This method was tested by analyzing the synthetic mixture of PG, GU, DP and CP. As a comparison method, a classsical HPLC method was used. The proposed methods were applied to syrups samples containing four drugs and the obtained results were statistically compared with each other. Finally, the main advantage of HPLC-PLS method over the classical HPLC method tried to emphasized as the using of simple mobile phase, shorter analysis time and no use of internal standard and gradient elution.     

HPLC and chemometrics-assisted UV-spectroscopy methods for the simultaneous determination of ambroxol and doxycycline in capsule

High-performance liquid chromatography (HPLC) and multivariate spectrophotometric methods are described for the simultaneous determination of ambroxol hydrochloride (AM) and doxycycline (DX) in combined pharmaceutical capsules. The chromatographic separation was achieved on reversed-phase C(18) analytical column with a mobile phase consisting of a mixture of 20mM potassium dihydrogen phosphate, pH 6-acetonitrile in ratio of (1:1, v/v) and UV detection at 245 nm. Also, the resolution has been accomplished by using numerical spectrophotometric methods as classical least squares (CLS), principal component regression (PCR) and partial least squares (PLS-1) applied to the UV spectra of the mixture and graphical spectrophotometric method as first derivative of the ratio spectra ((1)DD) method. Analytical figures of merit (FOM), such as sensitivity, selectivity, analytical sensitivity, limit of quantitation and limit of detection were determined for CLS, PLS-1 and PCR methods. The proposed methods were validated and successfully applied for the analysis of pharmaceutical formulation and laboratory-prepared mixtures containing the two component combination.     

Multicomponent determination of the pesticide naptalam and its metabolites in river water, by applying partial least squares calibration to the derivative spectrophotometric signals

A multivariate calibration method, partial least squares (types PLS-1 and PLS-2), was applied to the simultaneous determination of naptalam (N-(1-naphthyl) phthalamic acid) and its metabolites N-(1-naphthyl) phthalimide and 1-naphthylamine in mixtures by UV-visible absorption spectrophotometry. The absorption and first-derivative absorption spectra of mixtures were used to perform the optimization of the calibration matrices by the PLS method. Two different experimental designs for the three-component mixtures are assayed and the results are discussed. The proposed method with the derivative spectra was applied to the determination of these analytes in river water at the ppb level.     

Simultaneous determination of phenobarbital and phenytoin in tablet preparations by multivariate spectrophotometric calibration

The use of multivariate spectrophotometric calibration for the simultaneous determination of the active components of antiepileptic tablets is presented. The resolution of binary mixtures of phenobarbital and phenytoin has been accomplished by using partial least squares (PLS-1) regression analysis. Although the components show an important degree of spectral overlap, they have been simultaneously determined with high accuracy, with no interference from tablet excipients. A comparison is presented with the related multivariate method of classical least squares (CLS) analysis, which is shown to yield less reliable results due to the severe spectral overlap presented by the studied compounds. A statistical measure for the spectral overlap is proposed.     

Application of Multivariate Calibration Techniques to HPLC Data for Quantitative Analysis of a Binary Mixture of Hydrochlorathiazide and Losartan in Tablets

New multivariate approaches have been applied to high-performance liquid chromatography (HPLC) with multiwavelength photodiode-array (PDA) detection. Multivariate calibration techniques such as partial least squares (PLS), principal component regression (PCR), classical least squares (CLS), and inverse least squares (ILS) was subjected to HPLC data for simultaneous quantitative analysis of synthetic binary mixtures and a commercial tablet formulation containing hydrochlorothiazide (HCT) and losartan potassium (LST). The combined use of HPLC and multivariate calibrations has been denoted HPLC–CLS, HPLC–ILS, HPLC–PCR, and HPLC–PLS. Successful chromatographic separation of the two active compounds and enalapril maleate, used as internal standard (IS), was accomplished by means of a 4.6 mm i.d. × 250 mm, 5 m particle, Waters Symmetry C₁₈ reversed-phase column and a mobile phase consisting of 60:40 acetate buffer (0.2 M, pH 4.8)–acetonitrile (v/v, 60:40). HPLC data based on the ratio of analyte peak areas to IS peak area were obtained by PDA detection at five-wavelengths (250, 255, 260, 265, and 270 nm). The HPLC–CLS, HPLC–ILS, HPLC–PCR, and HPLC–PLS calibration plots for hydrochlorothiazide and losartan potassium were constructed separately by using the peak-area ratios corresponding to the concentrations of each active compound. The HPLC multivariate calibrations obtained were tested for different synthetic mixtures containing HCT and LST in the presence of the IS. These multivariate chromatographic methods were also applied to a commercial pharmaceutical dosage form containing HCT and LST. The results obtained from the multivariate calibrations were compared with those obtained by use of another, classical HPLC method using single-wavelength detection.Revised: 29 September 2004 and 4 January 2005