This paper described a rapid ultraviolet spectrophotometric assay for simultaneous determination ... more This paper described a rapid ultraviolet spectrophotometric assay for simultaneous determination of tetracyclines (TC + ETC) and their anhydroderivatives (ATC + EATC), by using third- or fourth-derivative spectra recorded on samples in ethanol or dioxane. The analytical procedures are based on linear relationships between specific peak-trough values and the relative concentrations of tetracycline and of ATC-EATC, in mixtures containing TC, ATC and EATC. The toxic EATC can be estimated about half of the anhydrotetracyclines concentration values. The determination limit of anhydroderivatives is 0.05%. A simple purity test of the antibiotic is also reported. Accuracy, precision and linearity are discussed. The method is particularly applicable to routine analysis of products containing TC, in bulk and in some pharmaceutical formulations.
A rapid derivative spectrophotometric method for the simultaneous determination of atenolol and c... more A rapid derivative spectrophotometric method for the simultaneous determination of atenolol and chlorthalidone. in antihyper-tens& specialities, is described. The analytical procedure is based on the linear relationship between the atenolol concentration and the minimum peak at 236 nm and that between the,chlorthalidone concentration and the two signals arising from the minimum peak at 236 nm and a peak-trough at 229-21X nm. Satisfactory values for the precision and accuracy of the method have been estimated.
An optimized model of multivariate classification for the monitoring of eighteen spring waters in... more An optimized model of multivariate classification for the monitoring of eighteen spring waters in the land of Serra St. Bruno, Calabria, Italy, has been developed. Thirty analytical parameters for each water source were investigated and reduced to eight by means of Principal Component Analysis (PCA). Water springs were grouped in five distinct classes by cluster techniques (CA) and a model for their classification was built by a Partial Least Squares-Discriminant Analysis (PLS-DA) procedure. The model was optimized and validated and then applied to new data matrices, containing the analytical parameters carried out on the same sources during the successive years. This model proved to be able to notice deviations of the global analytical characteristics, by pointing out in the course of time a different distribution of the samples within the classes. The variation of nitrate concentration was demonstrated to be the major responsible for the observed class shifts. The shifting sources were localized in areas used as sowable lands and high variability of nitrate content was ascribed to the practice of crop rotation, involving a varying use of the nitrogenous chemical fertilizers.
The improvement of barnidipine photostability was investigated in cyclodextrin or liposome matric... more The improvement of barnidipine photostability was investigated in cyclodextrin or liposome matrices and in appropriate combinations of these matrices. These supramolecular systems allowed the preparation of liquid formulations, as an alternative to the current solid commercial specialties. Materials & methods: Photodegradation stressing tests were performed according to the ICH rules and monitored by derivative spectrophotometry. Optimization was evaluated in terms of drug-inclusion efficiency. Results: The photodegradation rate of barnidipine in ethanol proved rapid (residual percentage of 29.81%) after a radiation exposure of 225 kJ/m 2 . The residual concentrations detected for liposome and cyclodextrin complexes were 42.90 and 72.03%, respectively. The best results were obtained when the drug-cyclodextrin complex was in turn entrapped in liposomes (residual percentage of 90.78%). Conclusion: The stability of the drug-in-cyclodextrin-in-liposome system increased significantly with a value close to that of solid formulations whose residual percentage was 96.03%.
An advanced and powerful chemometric approach is proposed for the analysis of incomplete multiset... more An advanced and powerful chemometric approach is proposed for the analysis of incomplete multiset data obtained by fusion of hyphenated liquid chromatographic DAD/MS data with UV spectrophotometric data from acid-base titration and kinetic degradation experiments. Column- and row-wise augmented data blocks were combined and simultaneously processed by means of a new version of the multivariate curve resolution-alternating least squares (MCR-ALS) technique, including the simultaneous analysis of incomplete multiset data from different instrumental techniques. The proposed procedure was applied to the detailed study of the kinetic photodegradation process of the amiloride (AML) drug. All chemical species involved in the degradation and equilibrium reactions were resolved and the pH dependent kinetic pathway described.
Light has been recognized as one of the most important external factors in drug instability and t... more Light has been recognized as one of the most important external factors in drug instability and the knowledge of photo-reactivity is essential in the overall profile of a drug. The drug photo-chemistry helps in the design of more photo-stable drugs as well as in the development of photo-protective systems. During the phases of drug design, investigation and prediction of the
A quantitative structure-property relationships (QSPR) model, correlating the light sensitivity a... more A quantitative structure-property relationships (QSPR) model, correlating the light sensitivity against theoretical molecular descriptors, was developed for a set of 1,4-dihydropyridine calcium channel antagonist drugs. These compounds are characterized by a high tendency to degradation when exposed to light, furnishing in the most of cases a related oxidation product from aromatization of the dihydropyridinic ring. Photodegradation was forced by exposing the drugs to a Xenon lamp, in accordance with the ICH international rules, and degradation kinetics was monitored by spectrophotometry.
Journal of Pharmaceutical and Biomedical Analysis, 2002
A derivative spectrophotometric method for the simultaneous determination of amlodipine and its p... more A derivative spectrophotometric method for the simultaneous determination of amlodipine and its pyridine photodegradation product has been developed. The analytes concentrations were linearly correlated with spectral measurements in the 3rd order UV derivative spectrum through equations obtained by simple and multiple regression analysis. The recovery values were estimated to range from 95 to 99% and the quantitation limit of the photoproduct was found to be equivalent to an impurity level of 1%, with respect to the content of amlodipine. The method could usefully be applied to routine quality control of pharmaceutical formulations containing amlodipine.
Journal of Pharmaceutical and Biomedical Analysis, 2014
A new approach to pre-processing of the UV spectral data in combination with chemometric techniqu... more A new approach to pre-processing of the UV spectral data in combination with chemometric techniques, aiming to obtain a significant amplification of the analytical information, is proposed. The single areas under the curve between two consecutive wavelengths were calculated along the full spectrum and therefore their cumulative sum was carried out. The method was called "cumulative area pre-processing" (CAP) and applied to multicomponent pharmaceutical formulations to test its performance in improving the accuracy of the analysis. The proposed procedure has demonstrated high ability in the quantitative determination of the components present in very low amount compared to other.
The simultaneous quantitative assay of 1,4-dihydropyridine calcium antagonist manidipine and its ... more The simultaneous quantitative assay of 1,4-dihydropyridine calcium antagonist manidipine and its main photodegradation byproduct has been defined by using a multivariate calibration on UV spectra based on a classical least squares regression. Optimization of the procedure was achieved by means of a calibration model using suitable wavelength ranges singled out from a fractionation scheme thereat defined. Recovery values of 99 and 96% for the drug and the by-product, respectively, were found either in appropriately prepared mixtures and commercial formulations. Quantification limit for the photoproduct concentration was estimated as 1.0% for the reference samples.
Multivariate curve resolution -alternating least squares (MCR-ALS) has been applied to data colle... more Multivariate curve resolution -alternating least squares (MCR-ALS) has been applied to data collected from UV spectrophotometric analysis of melatonin samples exposed to light with varying irradiance power. MCR-ALS was able to explain the degradation kinetics of this drug, deducing the pure spectra and concentration changes of the different species present throughout the entire process. Possible rotational ambiguities associated with MCR solutions were investigated and their extent was evaluated. The extent of the rotation ambiguity was estimated from the band boundaries of feasible solutions calculated using the MCR-BANDS procedure. The use of a non-linear fitting routine allowed improving kinetic information and provided a method of evaluation of the rate constants of the degradation process. The degradation pathway was found to follow a first-order reaction model, in which melatonin underwent photo-oxidation of the indole ring to give a formylamine group. Kinetics of the reaction was shown to be dependent on irradiation conditions, with an increase of the rate constants when light power also increased.
Chemometrics and Intelligent Laboratory Systems, 2009
The prediction power of different chemometric methods was compared when applied on ordinary UV sp... more The prediction power of different chemometric methods was compared when applied on ordinary UV spectra and first-to-fourth order derivative spectra. Principal component regression (PCR) and partial least squares with one dependent variable (PLS-1) and three dependent variables (PLS2) were applied on spectral data of pharmaceutical formulations containing paracetamol, propiphenazone and caffeine. Derivatization ability in resolving spectral overlapping was evaluated when the multivariate methods are adopted for analysis of multicomponent mixtures. The chemometric models were tested on an external validation dataset and finally applied to the analysis of commercial formulations containing two or three drugs. The models were optimized by selecting the wavelength regions to be used in calibration through a new method which ensured either an acquisition of useful information or a removal of redundant or noisy data. This procedure provided to evaluate the analytical information of the wavelengths by using the component regression coefficients calculated in multivariate regressions. Significant advantages were found in analysis of all the analytes when the calibration models from third-order derivative spectra were used, showing relative standard errors less than 1.4%. In contrast, the other derivative orders displayed higher variance and their use gave inaccurate results.
A sensitive HPLC-DAD method for the simultaneous determination of the anticancer lonidamine and f... more A sensitive HPLC-DAD method for the simultaneous determination of the anticancer lonidamine and five potential impurities in pure powder and tablet dosage forms was developed and validated. The impurities comprised by-products from thermal and photodegradation and potential secondary products from the drug synthesis. The structure of the main drug impurity was elucidated with the aid of GC-MS chromatography. A good resolution of all the analytes was achieved on a Gemini C18 column using isocratic elution and DAD detection. The optimal mobile phase consisted of a mixture of methanolphosphate buffer (pH 3) (80 : 20, v/v). At a flow rate of 1.5 ml min À1 , the total time of analysis was less than 15 min. The method was determined to be linear in the range of 10-200 mg ml À1 for the quantitation of lonidamine and 0.5-50 mg ml À1 for the related substances with a detection limit of 0.15 mg ml À1 for the impurities. Percentage recoveries ranged from 97.4 to 102.3 and 95.7 to 103.5 for the drug and impurities, respectively, and the relative precision values were less than 3.3%. Finally, the method was demonstrated to be robust, resistant to small variations of chromatographic variables such as pH, mobile phase organic/aqueous composition and column temperature.
This paper described a rapid ultraviolet spectrophotometric assay for simultaneous determination ... more This paper described a rapid ultraviolet spectrophotometric assay for simultaneous determination of tetracyclines (TC + ETC) and their anhydroderivatives (ATC + EATC), by using third- or fourth-derivative spectra recorded on samples in ethanol or dioxane. The analytical procedures are based on linear relationships between specific peak-trough values and the relative concentrations of tetracycline and of ATC-EATC, in mixtures containing TC, ATC and EATC. The toxic EATC can be estimated about half of the anhydrotetracyclines concentration values. The determination limit of anhydroderivatives is 0.05%. A simple purity test of the antibiotic is also reported. Accuracy, precision and linearity are discussed. The method is particularly applicable to routine analysis of products containing TC, in bulk and in some pharmaceutical formulations.
A rapid derivative spectrophotometric method for the simultaneous determination of atenolol and c... more A rapid derivative spectrophotometric method for the simultaneous determination of atenolol and chlorthalidone. in antihyper-tens& specialities, is described. The analytical procedure is based on the linear relationship between the atenolol concentration and the minimum peak at 236 nm and that between the,chlorthalidone concentration and the two signals arising from the minimum peak at 236 nm and a peak-trough at 229-21X nm. Satisfactory values for the precision and accuracy of the method have been estimated.
An optimized model of multivariate classification for the monitoring of eighteen spring waters in... more An optimized model of multivariate classification for the monitoring of eighteen spring waters in the land of Serra St. Bruno, Calabria, Italy, has been developed. Thirty analytical parameters for each water source were investigated and reduced to eight by means of Principal Component Analysis (PCA). Water springs were grouped in five distinct classes by cluster techniques (CA) and a model for their classification was built by a Partial Least Squares-Discriminant Analysis (PLS-DA) procedure. The model was optimized and validated and then applied to new data matrices, containing the analytical parameters carried out on the same sources during the successive years. This model proved to be able to notice deviations of the global analytical characteristics, by pointing out in the course of time a different distribution of the samples within the classes. The variation of nitrate concentration was demonstrated to be the major responsible for the observed class shifts. The shifting sources were localized in areas used as sowable lands and high variability of nitrate content was ascribed to the practice of crop rotation, involving a varying use of the nitrogenous chemical fertilizers.
The improvement of barnidipine photostability was investigated in cyclodextrin or liposome matric... more The improvement of barnidipine photostability was investigated in cyclodextrin or liposome matrices and in appropriate combinations of these matrices. These supramolecular systems allowed the preparation of liquid formulations, as an alternative to the current solid commercial specialties. Materials & methods: Photodegradation stressing tests were performed according to the ICH rules and monitored by derivative spectrophotometry. Optimization was evaluated in terms of drug-inclusion efficiency. Results: The photodegradation rate of barnidipine in ethanol proved rapid (residual percentage of 29.81%) after a radiation exposure of 225 kJ/m 2 . The residual concentrations detected for liposome and cyclodextrin complexes were 42.90 and 72.03%, respectively. The best results were obtained when the drug-cyclodextrin complex was in turn entrapped in liposomes (residual percentage of 90.78%). Conclusion: The stability of the drug-in-cyclodextrin-in-liposome system increased significantly with a value close to that of solid formulations whose residual percentage was 96.03%.
An advanced and powerful chemometric approach is proposed for the analysis of incomplete multiset... more An advanced and powerful chemometric approach is proposed for the analysis of incomplete multiset data obtained by fusion of hyphenated liquid chromatographic DAD/MS data with UV spectrophotometric data from acid-base titration and kinetic degradation experiments. Column- and row-wise augmented data blocks were combined and simultaneously processed by means of a new version of the multivariate curve resolution-alternating least squares (MCR-ALS) technique, including the simultaneous analysis of incomplete multiset data from different instrumental techniques. The proposed procedure was applied to the detailed study of the kinetic photodegradation process of the amiloride (AML) drug. All chemical species involved in the degradation and equilibrium reactions were resolved and the pH dependent kinetic pathway described.
Light has been recognized as one of the most important external factors in drug instability and t... more Light has been recognized as one of the most important external factors in drug instability and the knowledge of photo-reactivity is essential in the overall profile of a drug. The drug photo-chemistry helps in the design of more photo-stable drugs as well as in the development of photo-protective systems. During the phases of drug design, investigation and prediction of the
A quantitative structure-property relationships (QSPR) model, correlating the light sensitivity a... more A quantitative structure-property relationships (QSPR) model, correlating the light sensitivity against theoretical molecular descriptors, was developed for a set of 1,4-dihydropyridine calcium channel antagonist drugs. These compounds are characterized by a high tendency to degradation when exposed to light, furnishing in the most of cases a related oxidation product from aromatization of the dihydropyridinic ring. Photodegradation was forced by exposing the drugs to a Xenon lamp, in accordance with the ICH international rules, and degradation kinetics was monitored by spectrophotometry.
Journal of Pharmaceutical and Biomedical Analysis, 2002
A derivative spectrophotometric method for the simultaneous determination of amlodipine and its p... more A derivative spectrophotometric method for the simultaneous determination of amlodipine and its pyridine photodegradation product has been developed. The analytes concentrations were linearly correlated with spectral measurements in the 3rd order UV derivative spectrum through equations obtained by simple and multiple regression analysis. The recovery values were estimated to range from 95 to 99% and the quantitation limit of the photoproduct was found to be equivalent to an impurity level of 1%, with respect to the content of amlodipine. The method could usefully be applied to routine quality control of pharmaceutical formulations containing amlodipine.
Journal of Pharmaceutical and Biomedical Analysis, 2014
A new approach to pre-processing of the UV spectral data in combination with chemometric techniqu... more A new approach to pre-processing of the UV spectral data in combination with chemometric techniques, aiming to obtain a significant amplification of the analytical information, is proposed. The single areas under the curve between two consecutive wavelengths were calculated along the full spectrum and therefore their cumulative sum was carried out. The method was called "cumulative area pre-processing" (CAP) and applied to multicomponent pharmaceutical formulations to test its performance in improving the accuracy of the analysis. The proposed procedure has demonstrated high ability in the quantitative determination of the components present in very low amount compared to other.
The simultaneous quantitative assay of 1,4-dihydropyridine calcium antagonist manidipine and its ... more The simultaneous quantitative assay of 1,4-dihydropyridine calcium antagonist manidipine and its main photodegradation byproduct has been defined by using a multivariate calibration on UV spectra based on a classical least squares regression. Optimization of the procedure was achieved by means of a calibration model using suitable wavelength ranges singled out from a fractionation scheme thereat defined. Recovery values of 99 and 96% for the drug and the by-product, respectively, were found either in appropriately prepared mixtures and commercial formulations. Quantification limit for the photoproduct concentration was estimated as 1.0% for the reference samples.
Multivariate curve resolution -alternating least squares (MCR-ALS) has been applied to data colle... more Multivariate curve resolution -alternating least squares (MCR-ALS) has been applied to data collected from UV spectrophotometric analysis of melatonin samples exposed to light with varying irradiance power. MCR-ALS was able to explain the degradation kinetics of this drug, deducing the pure spectra and concentration changes of the different species present throughout the entire process. Possible rotational ambiguities associated with MCR solutions were investigated and their extent was evaluated. The extent of the rotation ambiguity was estimated from the band boundaries of feasible solutions calculated using the MCR-BANDS procedure. The use of a non-linear fitting routine allowed improving kinetic information and provided a method of evaluation of the rate constants of the degradation process. The degradation pathway was found to follow a first-order reaction model, in which melatonin underwent photo-oxidation of the indole ring to give a formylamine group. Kinetics of the reaction was shown to be dependent on irradiation conditions, with an increase of the rate constants when light power also increased.
Chemometrics and Intelligent Laboratory Systems, 2009
The prediction power of different chemometric methods was compared when applied on ordinary UV sp... more The prediction power of different chemometric methods was compared when applied on ordinary UV spectra and first-to-fourth order derivative spectra. Principal component regression (PCR) and partial least squares with one dependent variable (PLS-1) and three dependent variables (PLS2) were applied on spectral data of pharmaceutical formulations containing paracetamol, propiphenazone and caffeine. Derivatization ability in resolving spectral overlapping was evaluated when the multivariate methods are adopted for analysis of multicomponent mixtures. The chemometric models were tested on an external validation dataset and finally applied to the analysis of commercial formulations containing two or three drugs. The models were optimized by selecting the wavelength regions to be used in calibration through a new method which ensured either an acquisition of useful information or a removal of redundant or noisy data. This procedure provided to evaluate the analytical information of the wavelengths by using the component regression coefficients calculated in multivariate regressions. Significant advantages were found in analysis of all the analytes when the calibration models from third-order derivative spectra were used, showing relative standard errors less than 1.4%. In contrast, the other derivative orders displayed higher variance and their use gave inaccurate results.
A sensitive HPLC-DAD method for the simultaneous determination of the anticancer lonidamine and f... more A sensitive HPLC-DAD method for the simultaneous determination of the anticancer lonidamine and five potential impurities in pure powder and tablet dosage forms was developed and validated. The impurities comprised by-products from thermal and photodegradation and potential secondary products from the drug synthesis. The structure of the main drug impurity was elucidated with the aid of GC-MS chromatography. A good resolution of all the analytes was achieved on a Gemini C18 column using isocratic elution and DAD detection. The optimal mobile phase consisted of a mixture of methanolphosphate buffer (pH 3) (80 : 20, v/v). At a flow rate of 1.5 ml min À1 , the total time of analysis was less than 15 min. The method was determined to be linear in the range of 10-200 mg ml À1 for the quantitation of lonidamine and 0.5-50 mg ml À1 for the related substances with a detection limit of 0.15 mg ml À1 for the impurities. Percentage recoveries ranged from 97.4 to 102.3 and 95.7 to 103.5 for the drug and impurities, respectively, and the relative precision values were less than 3.3%. Finally, the method was demonstrated to be robust, resistant to small variations of chromatographic variables such as pH, mobile phase organic/aqueous composition and column temperature.
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Papers by Gaetano Ragno