Simultaneous spectrophotometric determination of chlorphenoxamine hydrochloride and caffeine in a pharmaceutical preparation using first derivative of the ratio spectra and chemometric methods

Three new methods are described for the simultaneous determination of chlorphenoxamine hydrochloride (CP) and caffeine (CAF) in their combination. In the first method, ratio spectra derivative spectrophotometry, analytical signals were measured at the wavelengths corresponding to either maxima and minima for both drugs in the first derivative spectra of the ratio spectra obtained by using each other spectra as divisor in their solution in 0.1 M HCl. In the other two methods, chemometric techniques, classical least-squares (CLS) and inverse least-squares (ILS), the concentration data matrix were prepared by using the synthetic mixtures containing these drugs in 0.1 M HCl. The absorbance data matrix corresponding to the concentration data matrix was obtained by the measurements of absorbances in the range 225-285 nm in the intervals with Deltalambda = 5 nm at 13 wavelengths in their zero-order spectra, then, calibration or regression was obtained by using the absorbance data matrix and concentration data matrix for the prediction of the unknown concentrations of CP and CAF in their mixture. The numerical values were calculated by using MAPLE V software in chemometric methods. The procedures do not require any separation step. The accuracy and the precision of the methods have been determined and they have been validated by analyzing synthetic mixtures containing title drugs. These three methods were successfully applied to a pharmaceutical formulation, sugar-coated tablet, and the results were compared with each other.     

Spectophotometric quantitative resolution of hydrochlorothiazide and spironolactone in tablets by chemometric analysis methods

Spectrophotometric simultaneous determination of hydrochlorothiazide and spironolactone in tablets was performed by classical least-squares (CLS), inverse least-squares (ILS), principal component regression (PCR) and partial least-squares (PLS). The methods of the chemometric analysis do not require sample pretreatment procedure. A training set of 25 standard mixture containing both drugs was prepared in the concentration range of 2-20 mug/ml according to mixture design. The multivarate calibrations were obtained by measuring the zero-order and first-derivative absorbances at 15 points from 220 to 290 nm using the training set. The validation of the multivariate methods was realised by analysing the synthetic mixtures of hydrochlorothiazide and spironolactone. The result obtained on the synthetic mixture and tablets were statistically compared by the one-way ANOVA test. The chemometrics analysis methods were satisfactorily applied to the simultaneous determination of hydrochlorothiazide and spironolactone in the pharmaceutical tablet formulation.     

Spectrophotometric quantitative determination of cilazapril and hydrochlorothiazide in tablets by chemometric methods

Four chemometric methods were applied to simultaneous determination of cilazapril and hydrochlorothiazide in tablets. Classical least-square (CLS), inverse least-square (ILS), principal component regression (PCR) and partial least-squares (PLS) methods do not need any priori graphical treatment of the overlapping spectra of two drugs in a mixture. For all chemometric calibrations a concentration set of the random mixture consisting of the two drugs in 0.1 M HCI and methanol (1:1) was prepared. The absorbance data in the UV-Vis spectra were measured for the 15 wavelength points (from 222 to 276 nm) in the spectral region 210-290 nm considering the intervals of deltalambda = 4 nm. The calibration of the investigated methods involves only absorbance and concentration data matrices. The developed calibrations were tested for the synthetic mixtures consisting of two drugs and using the Maple V software the chemometric calculations were performed. The results of the methods were compared each other as well as with HPLC method and a good agreement was found.     

Simultaneous spectrophotometric determination of cyproterone acetate and estradiol valerate in pharmaceutical preparations by ratio spectra derivative and chemometric methods

Ratio spectra derivative spectrophotometry and two chemometric methods (classical least squares, CLS and inverse least squares, ILS, were proposed for the simultaneous quantitative analysis of a binary mixture consists of cyproterone acetate (CA) and estradiol valerate (EV) in the commercial pharmaceutical preparations. In the ratio spectra derivative method, linear regression equations for both drugs were obtained by measuring the analytical signals at the wavelenghts corresponding to either maximums and minimums in the first derivative spectra of the ratio spectra. In the chemometric techniques, the concentration matrix was prepared by using the synthetic mixtures containing these drugs. The absorbance matrix corresponding to the concentration matrix was obtained by measuring the absorbances at 14 wavelengths in the range 220-290 nm for the zero-order spectra. Two chemometric calibrations were constructed by using the absorbance matrix and concentration matrix for the prediction of the unknown concentrations of CA and EV in their mixture. The numerical values were calculated by using 'MAPLE V' software. The accuracy and the precision of the methods have been determined and they have been validated by analyzing synthetic mixtures containing these two drugs. The proposed methods were successfully applied to a pharmaceutical formulation, sugar-coated tablet, and the results were compared with each other.     

Simultaneous spectrophotometric determination of pseudoephedrine hydrochloride and ibuprofen in a pharmaceutical preparation using ratio spectra derivative spectrophotometry and multivariate calibration techniques

Spectrophotometric methods are described for the simultaneous determination of pseudoephedrine hydrochloride and ibuprofen in their combination. The obtained data were evaluated by using five different methods. In the first method, ratio spectra derivative spectrophotometry, analytical signals were measured at the wavelengths corresponding to either maximums and minimums for both drugs in the first derivative spectra of the ratio spectra obtained by using each other spectra as divisor in their solution in 0.1 M HCl. In the other four spectrophotometric methods using chemometric techniques, classical least-squares, inverse least-squares, principal component regression and partial least-squares (PLS), the concentration data matrix were prepared by using the synthetic mixtures containing these drugs in methanol:0.1 M HCl (3:1). The absorbance data matrix corresponding to the concentration data matrix was obtained by the measurements of absorbances in the range 240-285 nm in the intervals with deltalambda = 2.5 nm at 18 wavelengths in their zero-order spectra, then, calibration or regression was obtained by using the absorbance data matrix and concentration data matrix for the prediction of the unknown concentrations of pseudoephedrine hydrochloride and ibuprofen in their mixture. The procedures did not require any separation step. The linear range was found to be 300-1300 microg/ml for ibuprofen and 100-1300 microg/ml for pseudoephedrine hydrochloride in all five methods. The accuracy and the precision of the methods have been determined and they have been validated by analyzing synthetic mixtures. The five methods were successfully applied to tablets and the results were compared with each other.     

Two new spectrophotometric approaches to the multicomponent analysis of the acetaminophen and caffeine in tablets by classical least-squares and principal component regression techniques

Classical least-squares (CLS) and principal component regression (PCR) techniques were proposed for the simultaneous analysis of tablets containing acetaminophen and caffeine without using a chemical separation procedure. The chemometric calibrations were prepared by measuring the absorbances values at the 15 wavelengths in the spectral region 215-285 nm and by using a training set of the mixtures of both drugs in 0.1 M HCI. The obtained chemometric calibrations were used for the estimation of acetaminophen and caffeine in samples. The numerical calculations were performed with the 'MAPLE V' software. By applying two techniques to synthetic mixtures, the mean recoveries and the relative standard deviations in the CLS and PCR techniques were found as 99.5 and 1.29, 99.7 and 1.00% for acetaminophen and 99.9 and 1.92, 100.0 and 1.178% for caffeine, respectively. Our results were compared with those obtained previously by one of us considering HPLC method as a reference method. These two methods were successfully applied to a pharmaceutical tablet formulation of two drugs.     

Dissolution and assaying of multicomponent tablets by chemometric methods using computer-aided spectrophotometer

Dissolution of three component tablets containing paracetamol (APAP), propyphenazone (PP), and caffeine (CAF) was carried out by USP paddle method. Three chemometric methods; inverse least square (ILS), principal component regression (PCR) and partial least squares (PLS) were applied to simultaneous assay of APAP, PP and CAF in tablets. The PCR, PLS and ILS methods were applied to simultaneous dissolution APAP, PP and CAF in tablets using a double beam UV-Vis spectrophotometer without any chemical separation and any graphical treatment of the overlapping spectra of three drugs. Twenty two mixture solutions in different concentrations were prepared in simulated gastric juice (SGJ, USP) for the chemometric calibrations as training set. The absorbance data matrix was obtained by measuring the absorbance at 14 wavelength points (from 222.5 to 292.5 nm) with the intervals of 5 nm (Deltalambda=5 nm) in the spectral region between 200 and 310 nm. Training set and absorbance data were used for the calibrations of chemometric methods. The developed calibrations were tested for the previously prepared solutions of mixture of three drugs for the validation of the assay method. The chemometric calculations were performed by using the 'MAPLE VRSQUO; software. The results of three chemometric methods were statistically compared with each other. These chemometric calibrations were successfully applied to the content uniformity and dissolution of the multicomponent tablets without any separation procedure. The synthetic mixtures of three drugs were used for the validity of the calibrations. Means recoveries (percent) and relative standard deviation of PLS, PCR and ILS methods were found to be 100.1+/-0.6, 101.4+/-1.6 and 100.1+/-0.6 for APAP; 100.9+/-3.2, 102.0+/-3.3 and 100.9+/-3.2 for PP; 99.9+/-3.5, 101.6+/-3.3 and 99.9+/-3.2 for CAF, respectively. Dissolution profiles of three component tablets were performed. More than 95% of drugs were dissolved within 15 min. All of the three-chemometric methods in this study can be satisfactorily used for the quantitative analysis and for dissolutions test of multicomponent dosage form.     

Simultaneous spectrophotometric determination of losartan potassium, amlodipine besilate and hydrochlorothiazide in pharmaceuticals by chemometric methods

In the present work, four different spectrophotometric methods for simultaneous estimation of losartan potassium, amlodipine besilate and hydrochlorothiazide in raw materials and in formulations are described. Overlapped data was quantitatively resolved by using chemometric methods, classical least squares (CLS), multiple linear regression (MLR), principal component regression (PCR) and partial least squares (PLS). Calibrations were constructed using the absorption data matrix corresponding to the concentration data matrix, with measurements in the range of 230.5-350.4 nm (Δλ = 0.1 nm) in their zero order spectra. The linearity range was found to be 8-40, 1-5 and 3-15 μg mL-1 for losartan potassium, amlodipine besilate and hydrochlorothiazide, respectively. The validity of the proposed methods was successfully assessed for analyses of drugs in the various prepared physical mixtures and in tablet formulations.     

Simultaneous spectrofluorimetric and spectrophotometric determination of melatonin and pyridoxine in pharmaceutical preparations by multivariate calibration methods

Partial least-squares (PLS) calibration and principal component regression (PCR) methods were utilized for the simultaneous spectrofluorimetric and spectrophotometric determination of pyridoxine (PY) and melatonin (MT). Since emission and adsorption spectra of these drugs overlap, PY and MT cannot be directly determined by fluorimetric nor by spectrophotometric methods. Full-spectrum multivariate calibration PLS and PCR methods were developed for both fluorimetry and spectrophotometry. The conditions were optimized for fluorimetric as well as for spectrophotometric determination of both drugs. The simultaneous determination of PY and MT was carried out in mixtures by recording the emission fluorescence spectrum between 324 and 500 nm (lambda(ex) 285 nm) for fluorimetry, and by recording the absorption spectrum between 250 and 350 nm for spectrophotometry (lambda(max(PY)) 310 nm, lambda(max(MT)) 278 nm). The experimental calibration matrixes were designed orthogonally. At the optimum conditions, dynamic ranges were 0.04-1.3 and 0.1-4 microg ml(-1) for fluorimetry and 1-22 and 1-24 microg ml(-1) for spectrophotometry for MT and PY, respectively. The calibration concentrations were prepared in the dynamic ranges. The parameters of the chemometrics procedure for the simultaneous determination of MT and PY were optimized, and the proposed methods were validated with prediction set. Finally the procedures were successfully applied to simultaneous spectrofluorimetric and spectrophotometric determination of PY and MT in synthetic mixtures and in a pharmaceutical formulation.     

Chemometric resolution of a mixture containing hydrochlorothiazide and amiloride by absorption and derivative spectrophotometry

Four chemometric techniques, classical least squares (CLS) and inverse least squares (ILS) and principal component regression (PCR) and partial least squares regression (PLSR) were applied to the absorption and derivative spectrophotometric determinations of amiloride and hydrochlorothiazide in a pharmaceutical preparation. Four chemometric calibrations for both zero-order and first derivative spectra were constructed by measuring the absorbance and their dA/dlambda values at 34 points in the wavelength range 205-395 nm for a training set containing 2-10 microg/ml amiloride and 4-28 microg/ml hydrochlorothiazide corresponding to 25 point mixture design. The building chemometric calibrations were confirmed by using the synthetic mixtures containing two drugs. The results obtained by the proposed techniques based on the use of the measurements at the absorption spectra and at the first derivative spectra were statistically compared with each other.     

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.     

Simultaneous estimation of ramipril, acetylsalicylic acid and atorvastatin calcium by chemometrics assisted UV-spectrophotometric method in capsules

In the present work, three different spectrophotometric methods for simultaneous estimation of ramipril, aspirin and atorvastatin calcium in raw materials and in formulations are described. Overlapped data was quantitatively resolved by using chemometric methods, viz. inverse least squares (ILS), principal component regression (PCR) and partial least squares (PLS). Calibrations were constructed using the absorption data matrix corresponding to the concentration data matrix. The linearity range was found to be 1-5, 10-50 and 2-10 μg mL-1 for ramipril, aspirin and atorvastatin calcium, respectively. The absorbance matrix was obtained by measuring the zero-order absorbance in the wavelength range between 210 and 320 nm. A training set design of the concentration data corresponding to the ramipril, aspirin and atorvastatin calcium mixtures was organized statistically to maximize the information content from the spectra and to minimize the error of multivariate calibrations. By applying the respective algorithms for PLS 1, PCR and ILS to the measured spectra of the calibration set, a suitable model was obtained. This model was selected on the basis of RMSECV and RMSEP values. The same was applied to the prediction set and capsule formulation. Mean recoveries of the commercial formulation set together with the figures of merit (calibration sensitivity, selectivity, limit of detection, limit of quantification and analytical sensitivity) were estimated. Validity of the proposed approaches was successfully assessed for analyses of drugs in the various prepared physical mixtures and formulations.     

Comparative study of the continuous wavelet transform, derivative and partial least squares methods applied to the overlapping spectra for the simultaneous quantitative resolution of ascorbic acid and acetylsalicylic acid in effervescent tablets

The simultaneous spectrophotometric determination of ascorbic acid (AA) and acetylsalicylic acid (ASA) in effervescent tablets in the presence of the overlapping spectra was accomplished by the continuous wavelet transform (CWT), derivative spectrophotometry (DS) and partial least squares (PLS) approaches without using any chemical pre-treatment. CWT and DS calibration equations for AA and ASA were obtained by measuring the CWT and DS amplitudes corresponding to zero-crossing points of spectra obtained by plotting continuous wavelet coefficients and first-derivative absorbance values versus the wavelengths, respectively. The PLS calibration was constructed by using the concentration set and its full absorbance data consisting of 850 points from 220 to 305 nm in the range of 210-310 nm. These three methods were tested by analyzing the synthetic mixtures of the above drugs and they were applied to the real samples containing two commercial pharmaceutical preparations of subjected drugs. A comparative study was carried out by using the experimental results obtained from three analytical methodologies and precise and accurate results were obtained.     

Spectrophotometric multicomponent resolution of a veterinary formulation containing oxfendazole and oxyclozanide by multivariate calibration-prediction techniques

Four multivariate calibration-prediction techniques, classical least-squares, inverse least-squares, principal component regression and partial least-squares regression were applied to the spectrophotometric multicomponent analysis of a veterinary formulation containing oxfendazole (OXF) and oxyclozanide (OXC) without any separation step. The multivariate calibrations were constructed by measuring the absorbance values at 14 points in the 285-350 nm wavelength range and by using the training set of standard mixtures containing OXF and OXC in the different compositions. The validity of building multivariate calibrations was checked by using the synthetic mixtures of both drugs. The multivariate calibration models were successfully applied to the spectrophotometric determination of OXF and OXC in laboratory prepared mixtures and a veterinary formulation. The results obtained were statistically compared with each other.     

Multivariate analysis of paracetamol, propiphenazone, caffeine and thiamine in quaternary mixtures by PCR, PLS and ANN calibrations applied on wavelet transform data

The quantitative resolution of a quaternary pharmaceutical mixture consisting of paracetamol, propiphenazone, caffeine and thiamine was performed by the simultaneous use of fractional wavelet transform (FWT) with principal component regression (PCR), partial least squares (PLS) and artificial neural networks (ANN) methods. A calibration set consisting of 22 mixture solutions was prepared by means of an orthogonal experimental design and their absorption spectra were recorded in the spectral range of 210.0–312.3 nm and then transferred into the fractional wavelet domain and processed by FWT. The chemometric calibrations FWT–PCR, FWT–PLS and FWT–ANN were computed by using the relationship between the coefficients provided by FWT method and the concentration data from calibration set. An external validation was carried out by applying the developed methods to the analysis of synthetic mixtures of the related compounds, obtaining successful results. The models were finally used to assay the studied drugs in the commercial pharmaceutical formulations.     

Simultaneous determination of Fe(II) and Fe(III) in pharmaceutical formulations with chromogenic mixed reagent by using principal component artificial neural network and multivariate calibration

The use of chemometric approaches for the simultaneous determination of Fe(II) and Fe(III) ions has been explored by means of a two component reagent. Mixed reagents of 1,10-phenanthroline and thiocyanate were used as a selective chromogenic system for speciation of Fe(II) and Fe(III). Although the complexes of Fe(II) and Fe(III) with mixed reagent show a spectral overlap, they have been simultaneously determined with chemometric approaches, such as principal component artificial neural network (PC-ANN), principal component regression (PCR) and partial least squares (PLS). A set of synthetic mixtures of Fe(II) and Fe(III) was evaluated and the results obtained by the applications of these chemometric approaches were discussed and compared. It was found that the PC-ANN and PLS methods afforded better precision relatively than its of PCR. PC-ANN and PLS methods were also applied satisfactorily in determination of Fe(II) and Fe(III) in pharmaceutical samples.     

Chemometric determination of amiloride hydrochloride, atenolol, hydrochlorothiazide and timolol maleate in synthetic mixtures and pharmaceutical formulations

Different chemometric methods such as classical least squares (CLS), principal components regression (PCR) and partial least squares with one dependent variable (PLS-1) applied on UV spectral data (0 D) and on their first derivatives (1 D) were evaluated for the simultaneous quantification of samples containing mixtures of amiloride hydrochloride, atenolol, hydrochlorothiazide and timolol maleate. Their performances were compared by means of ANOVA tests, which evidenced that 0 D-PCR, 0D-PLS-1, 1D-PCR, 1D-PLS-1, were reproducible and gave statistically similar results, while 0 D-CLS and 1D-CLS displayed higher variances than the former and failed to comply with the Levene's variance homogeneity test at different stages of the method comparison and validation process. The four statistically equivalent procedures were successfully applied to the analysis of synthetic samples with two to four analytes and to commercial tablet preparations containing amiloride hydrochloride and hydrochlorothiazide alone or in association with atenolol or timolol maleate.     

Evaluation of chemometric algorithms in quantitative X-ray powder diffraction (XRPD) of intact multi-component consolidated samples

Quantitative X-ray powder diffraction (XRPD) data obtained from intact, consolidated samples affords the opportunity to analyze mixtures that simulate pharmaceutical drug products without the need for reversion back to powders; an analytical preparation step that destroys the contextual solid-state information intrinsic to intact consolidated samples. Traditional, standardless quantitative methods generally involve sophisticated pattern refinement procedures (e.g., Rietveld refinement) and are limited to crystalline materials. Methods that incorporate an internal standard are not optimal for compact analysis, and may often be susceptible to prediction errors associated with intensity attenuation. Chemometric-based XRPD utilizes full-pattern methods that combine analyses of both Bragg diffraction and diffuse scatter, thereby allowing for enhancement of signal-to-noise, sensitivity, and selectivity. Classical least-squares (CLS) regression, principal components regression (PCR) and partial least squares (PLS) regression are three chemometric algorithms commonly employed in spectroscopy. In the present work, quantification of a consolidated four-component system, composed of two crystalline materials and two disordered materials was analyzed intact, using two different XRPD optics geometries. Calibrations constructed for the prediction of individual constituent concentrations using the aforementioned three multi-variate algorithms were statistically compared with traditional diffraction–absorption univariate calibration. PLS regression modeling of data collected in transmission geometry provided the best statistical results for the quantification of constituent concentration. Further, this calibration was minimally affected by diffraction pattern anomalies traditionally corrected prior to phase quantification.     

Content uniformity and dissolution tests of triplicate mixtures by a double divisor-ratio spectra derivative method

The use of a UV double divisor-ratio spectra derivative calibration for the simultaneous analysis of synthetic samples and commercial tablet preparations without prior separation is proposed. The method was successfully applied to quantify three ternary mixtures, chlorpheniramine maleate and caffeine combined with paracetamol or acetylsalicylic acid and a mixture of acetylsalicylic acid combined with paracetamol and caffeine, using the information in the absorption spectra of appropriate solutions. Beer's law was obeyed in the concentration range of 0.84-4.21 microg/ml for chlorpheniramine maleate, 1.60-15.96 microg/ml for caffeine, 2.0-20.0 microg/ml for acetylsalicylic acid and 1.58-15.93 microg/ml for paracetamol. The whole procedure was applied to synthetic mixtures of pure drugs as well as to commercial preparations (Algon) by using content uniformity and dissolution tests (USP 24) and was found to be precise and reproducible. According to the dissolution profile test more than 84% of paracetamol and caffeine were dissolved within 20 min. Acetylsalicylic acid dissolved more slowly, taking about 45-60 min to dissolve completely. A chemometric method partial least squares (PLS) and a HPLC method were also employed to evaluate the same mixtures. The results of the proposed method were in excellent agreement with those obtained from PLS and HPLC methods and can be satisfactorily used for routine analysis of multicomponent dosage forms.