Patricia Castellano - Academia.edu (original) (raw)
Papers by Patricia Castellano
The stability of pridinol mesylate (PRI) was investigated under different stress conditions, incl... more The stability of pridinol mesylate (PRI) was investigated under different stress conditions, including hydrolytic, oxidative, photolytic and thermal, as recommended by the ICH guidelines. Relevant degradation was found to take place under acidic (0.1N HCl) and photolytic (visible and long-wavelength UV-light) conditions, both yielding the product resulting from water elimination (ELI), while submission to an oxidizing environment gave the N-oxidation derivative (NOX). The standards of these degradation products were synthesized and characterized by IR, 1 H and 13 C NMR spectroscopy. A simple, sensitive and specific HPLC method was developed for the quantification of PRI, ELI and NOX in bulk drug, and the conditions were optimized by means of a statistical design strategy. The separation employs a C 18 column and a 51:9:40 (v/v/v) mixture of MeOH, 2-propanol and potassium phosphate solution (50 mM, pH 6.0), as mobile phase, delivered at 1.0 ml min −1 ; the analytes were detected and quantified at 220 nm. The method was validated, demonstrating to be accurate and precise (repeatability and intermediate precision levels) within the corresponding linear ranges of PRI (0.1-1.5 mg ml −1 ; r = 0.9983, n = 18) and both impurities (0.1-1.3% relative to PRI, r = 0.9996 and 0.9995 for ELI and NOX, respectively, n = 18). Robustness against small modifications of pH and percentage of the aqueous mobile phase was ascertained and the limits of quantification of the analytes were also determined (0.4 and 0.5 g ml −1 ; 0.04% and 0.05% relative to PRI for ELI and NOX, respectively). Peak purity indices (>0.9997), obtained with the aid of diode-array detection, and satisfactory resolution (R s > 2.0) between PRI and its impurities established the specificity of the determination, all these results proving the stability-indicating capability of the method. The kinetics of the degradation of PRI in acid medium was also studied, determining that this is a first-order process with regards to drug concentration, with an activation energy of 25.5 Kcal mol −1 and a t 1/2 = 10,830 h, in 0.1N HCl at 38 • C.
Journal of Liquid Chromatography Amp Related Technologies, Nov 1, 2011
Journal of Liquid Chromatography Amp Related Technologies, 2012
Journal of Pharmaceutical and Biomedical Analysis
A simple and reliable reversed-phase high-perfomance liquid chromatographic method has been devel... more A simple and reliable reversed-phase high-perfomance liquid chromatographic method has been developed and validated for the simultaneous determination of meloxicam and pridinol mesylate in their synthetic mixtures and combined tablet formulations. Both drugs were separated on a 250mm×4.6mm C18 column packed with 5 �m particles. The mobile phase, optimized through an experimental design, was a 51:9:40 (v/v/v) mixture of methanol, isopropanol and 50mM potassium phosphate buffer (pH 5.9), pumped at a flow rate of 1.0 ml min−1. UV detection was performed at 225 nm. The method was validated in the sample concentration ranges of 33.7–61.8 mg l−1 for meloxicam and 8.8–16.8 mg l−1 for pridinol mesylate, where it demonstrated good linearity with r = 0.9989 and 0.9987 (n = 15), respectively. The assay was shown to be repeatable at concentration levels of 70%, 100% and 130%, with relative standard deviation values of 1.09% and 0.82% for meloxicam and pridinol, respectively. For independent 100...
International Journal of Pharmaceutics, 2009
A simple chemometric approach to differentiate among the three crystalline polymorphs of the mode... more A simple chemometric approach to differentiate among the three crystalline polymorphs of the model drug Furosemide (FUR) in a pharmaceutical dosage form is presented. The proposed method is based on the principal component analysis with confidence regions (PCA-CR) comparison of the dissolution profiles of the test pharmaceutical formulation, and formulations containing the different polymorphs, employed as the corresponding references.
Journal of Pharmaceutical and Biomedical Analysis, 2011
A photostability study of Valsartan (VAL) is reported. Exposure of the drug to UV-vis radiation (... more A photostability study of Valsartan (VAL) is reported. Exposure of the drug to UV-vis radiation ( > 320 nm) yielded two previously unknown compounds, which were detected by HPLC. Preparative amounts of the new potential degradation products (DP-1 and DP-2) were obtained by submitting VAL bulk drug to extensive photodegradation. The impurities were isolated by preparative normal phase column chromatography. Analytical information from the infrared, nuclear magnetic resonance and mass spectral data of the degradation products revealed their structures as N-[2 -(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-N-isobutylpentanamide (DP-1) and N-(diazirino[1,3f]phenanthridin-4-ylmethyl)-N-isobutylpentanamide (DP-2). DP-1 arose from decarboxylation of VAL, while DP-2 results from further loss of nitrogen from the tetrazole motif of DP-1, with concomitant cyclization to yield a tetracyclic diazacyclopropene derivative.
Journal of Pharmaceutical and Biomedical Analysis, 2008
The stability of pridinol mesylate (PRI) was investigated under different stress conditions, incl... more The stability of pridinol mesylate (PRI) was investigated under different stress conditions, including hydrolytic, oxidative, photolytic and thermal, as recommended by the ICH guidelines. Relevant degradation was found to take place under acidic (0.1N HCl) and photolytic (visible and long-wavelength UV-light) conditions, both yielding the product resulting from water elimination (ELI), while submission to an oxidizing environment gave the N-oxidation derivative (NOX). The standards of these degradation products were synthesized and characterized by IR, 1 H and 13 C NMR spectroscopy. A simple, sensitive and specific HPLC method was developed for the quantification of PRI, ELI and NOX in bulk drug, and the conditions were optimized by means of a statistical design strategy. The separation employs a C 18 column and a 51:9:40 (v/v/v) mixture of MeOH, 2-propanol and potassium phosphate solution (50 mM, pH 6.0), as mobile phase, delivered at 1.0 ml min −1 ; the analytes were detected and quantified at 220 nm. The method was validated, demonstrating to be accurate and precise (repeatability and intermediate precision levels) within the corresponding linear ranges of PRI (0.1-1.5 mg ml −1 ; r = 0.9983, n = 18) and both impurities (0.1-1.3% relative to PRI, r = 0.9996 and 0.9995 for ELI and NOX, respectively, n = 18). Robustness against small modifications of pH and percentage of the aqueous mobile phase was ascertained and the limits of quantification of the analytes were also determined (0.4 and 0.5 g ml −1 ; 0.04% and 0.05% relative to PRI for ELI and NOX, respectively). Peak purity indices (>0.9997), obtained with the aid of diode-array detection, and satisfactory resolution (R s > 2.0) between PRI and its impurities established the specificity of the determination, all these results proving the stability-indicating capability of the method. The kinetics of the degradation of PRI in acid medium was also studied, determining that this is a first-order process with regards to drug concentration, with an activation energy of 25.5 Kcal mol −1 and a t 1/2 = 10,830 h, in 0.1N HCl at 38 • C.
Journal of Pharmaceutical and Biomedical Analysis, 2001
A numerical method, based on the use of spectrophotometric data coupled to PLS-1 multivariate cal... more A numerical method, based on the use of spectrophotometric data coupled to PLS-1 multivariate calibration, is reported for the simultaneous determination of furosemide and amiloride hydrochloride in synthetic samples and commercial tablets. The method was applied in the concentration ranges of 8.0-13.0 mg l − 1 for furosemide and 1.0-1.6 mg l − 1 for amiloride hydrochloride. Its accuracy and precision were determined, and it was validated by the analysis of synthetic mixtures of both drugs. The method was successfully applied to the quantitation of furosemide and amiloride hydrochloride in three different pharmaceutical formulations, providing results in agreement with those obtained by HPLC. It allowed the rapid, accurate and precise simultaneous estimation of the concentration of both analytes of interest in spite of their important spectral overlap, high concentration relationship and the presence of small amounts of different, unmodelled, absorbing excipients.
Journal of Pharmaceutical and Biomedical Analysis, 2007
An alternative method for the determination of fexofenadine (FEX) and pseudoephedrine (PSE) in th... more An alternative method for the determination of fexofenadine (FEX) and pseudoephedrine (PSE) in their combined tablet formulation has been developed, employing the partial least squares (PLS) analysis of spectral data of the analytes in their pharmaceutical association. A full-factorially designed set of 16 synthetic samples was employed for calibration purposes. The calibration models were constructed with wavelengths selection, in the ultraviolet region, according to their predictive ability. These were validated internally by the leave-one-out procedure and externally, employing appropriate sets of validation samples. The described method was linear for both analytes, over the range 160.6-301.2 mg L −1 for FEX (R 2 = 0.9993) and between 325.6 and 610.5 mg L −1 for PSE (R 2 = 0.9992). It was accurate, exhibiting 99.8% and 99.9% drug recoveries for FEX and PSE, respectively (N = 9), while in the intermediate precision experiment relative standard deviations were 1.4% for FEX and 1.2% for PSE.
Journal of Pharmaceutical and Biomedical Analysis, 2002
The use of multivariate spectrophotometric calibration for the simultaneous analysis of synthetic... more The use of multivariate spectrophotometric calibration for the simultaneous analysis of synthetic samples and commercial tablet preparations containing hydrochlorothiazide (HCT) and amiloride hydrochloride (AMH) is reported. Partial least squares (PLS-1) analysis of electronic absorption spectral data allowed the rapid and accurate resolution of mixtures in which the analyte ratios were approximately 10:1, without the need of a previous separation step and without interference from other sample constituents. The method, validated by the analysis of synthetic mixtures of both drugs, where accuracy over the linear working range as well as inter-and intra-assay precision were determined, was used in the concentration ranges of 21.7 Á/30.4 mg l (1 for HCT and 1.8 Á/3.0 mg l (1 for AMH. The proposed method was successfully applied to the evaluation of the stability of the stock solutions of the analytes in MeOH Á/H 2 O and to the elaboration of drug dissolution profiles of commercial tablets, results being concordant with those furnished by the USP technique. The method was also employed for the determination of drug content in two different pharmaceutical formulations, providing results that were in excellent agreement with those obtained by HPLC. #
Journal of Pharmaceutical and Biomedical Analysis, 2004
Different chemometric methods such as classical least squares (CLS), principal components regress... more 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, 0 D-PLS-1, 1 D-PCR and 1 D-PLS-1 were reproducible and gave statistically similar results, while 0 D-CLS and 1 D-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. .ar (T.S. Kaufman).
Journal of Liquid Chromatography & Related Technologies, 2010
Journal of Liquid Chromatography & Related Technologies, 2012
European Journal of Pharmaceutical Sciences, 2008
Acetaminophen Furosemide Multivariate method a b s t r a c t A new approach for testing batch "si... more Acetaminophen Furosemide Multivariate method a b s t r a c t A new approach for testing batch "similarity" through comparison of drug dissolution profiles, based on principal component analysis with the establishment of a confidence region (PCA-CR), is presented. The dissolution curves corresponding to three brands each of Furosemide and Acetaminophen tablets, taken as model drugs, were prepared by dissolution measurements at multiple pre-specified time points. Reference and test data were simultaneously subjected to PCA and pairwise comparisons between the dissolution characteristics of lots of the same and different brands were carried out. The comparisons involved plotting the weighed scores of the first two principal components of reference and test lots, while decision about "similarity" was made by checking for inclusion of more than 80% of the tablets of the test lot in the 95% confidence ellipse of the reference samples. Two published datasets were also analyzed in the same fashion and all the results were compared with information provided by the difference (f 1 ) and similarity (f 2 ) factor tests. Unlike the f 2 criterion, the proposed method reflects variability within the individual dissolution curves, being also highly sensitive to profile (shape and size) variations. Comparison between the area enclosed by the confidence ellipses of the weighed scores plot and the region obtained from the bootstrap-calculated acceptable values of the corresponding f 2 tests suggested that PCA-CR represents, in general, a more discriminating standard.
![Research paper thumbnail of Synthesis of 3H-spiro[benzofuran-2,1′-cyclohexane] derivatives from naturally occurring filifolinol and their classical complement pathway inhibitory activity](https://attachments.academia-assets.com/42585732/thumbnails/1.jpg)
](Bioorganic & Medicinal Chemistry Letters, 2006
Six 3H-spiro[benzofuran-2,1 0 -cyclohexane] derivatives were synthesized from naturally occurring... more Six 3H-spiro[benzofuran-2,1 0 -cyclohexane] derivatives were synthesized from naturally occurring filifolinol, and their classical complement pathway inhibitory activity was determined. IC 50 values of the most potent compounds were comparable to the activity of the natural complement inhibitor K76-COOH and some synthetic tricyclic analogs of it.
Analytical and Bioanalytical Chemistry, 2008
A convenient new method for the simultaneous determination of losartan potassium and hydrochlorot... more A convenient new method for the simultaneous determination of losartan potassium and hydrochlorothiazide, with minimum sample pretreatment, is described. The procedure, based on the multivariate analysis of spectral data in the 220−274 nm region by the partial least squares algorithm, is linear in the concentration range 1.06− 5.70 mg L −1 for hydrochlorothiazide and 4.0−22.2 mg L −1 for losartan. It is simple, rapid and robust, allowing accurate and precise results, with drug recovery rates of 99.3 and 100.4% and relative standard deviations of 1.7 and 1.0% obtained for hydrochlorothiazide and losartan, respectively. The method was applied to the simultaneous determination of both analytes in tablets, and it provided good results which were in statistical agreement with those provided by independent HPLC analyses of the samples. The method has also been successfully applied for the construction of drug dissolution profiles of a commercial pharmaceutical preparation containing both analytes.
Analytical and Bioanalytical Chemistry, 2003
A new, repeatable, and rapid method has been developed for resolution of binary mixtures of aceta... more A new, repeatable, and rapid method has been developed for resolution of binary mixtures of acetaminophen and diclofenac with minimum sample pretreatment and without separation of the analytes. The method, based on the PLS1 processing of absorbance data in the UV region, was successfully used for quantification of the drug content of three tablet preparations. The results obtained were in good agreement with HPLC recovery data. The method also enabled determination of drug-dissolution profiles of these commercial tablets, by simultaneous determination of both analytes during the dissolution test.
Analytical and Bioanalytical Chemistry, 2006
Two new analytical methods have been developed as convenient and useful alternatives for simultan... more Two new analytical methods have been developed as convenient and useful alternatives for simultaneous determination of hydrochlorothiazide (HCT) and propranolol hydrochloride (PRO) in pharmaceutical formulations. The methods are based on the first derivative of ratio spectra (DRS) and on partial least squares (PLS) analysis of the ultraviolet absorption spectra of the samples in the 250-350-nm region. The methods were calibrated between 8.7 and 16.0 mg L −1 for HCT and between 14.0 and 51.5 mg L −1 for PRO. An asymmetric full-factorial design and wavelength selection (277-294 nm for HCT and 297-319 for PRO) were used for the PLS method and signal intensities at 276 and 322 nm were used in the DRS method for HCT and PRO, respectively. Performance characteristics of the analytical methods were evaluated by use of validation samples and both methods showed to be accurate and precise, furnishing near quantitative analyte recoveries (100.4 and 99.3% for HCT and PRO by use of PLS) and relative standard deviations below 2%. For PLS the lower limits of quantification were 0.37 and 0.66 mg L −1 for HCT and PRO, respectively, whereas for DRS they were 1.15 and 3.05 mg L −1 for HCT and PRO, respectively. The methods were used for quantification of HCT and PRO in synthetic mixtures and in two commercial tablet preparations containing different proportions of the analytes. The results of the drug content assay and the tablet dissolution test were in statistical agreement (p<0.05) with those furnished by the official procedures of the USP 29. Preparation of dissolution profiles of the combined tablet formulations was also performed with the aid of the proposed methods. The methods are easy to apply, use relatively simple equipment, require minimum sample pre-treatment, enable high sample throughput, and generate less solvent waste than other procedures.
Analytica Chimica Acta, 2009
A simple high performance liquid chromatographic method for the determination of process-related ... more A simple high performance liquid chromatographic method for the determination of process-related impurities in bulk drug of the central anticholinergic compound pridinol mesylate, has been developed and validated. Spectroscopically characterized synthetic impurities were used as standards. The chromatographic separation was optimized employing an experimental design strategy, and was achieved on a C 18 column with a mobile phase containing 50 mM potassium phosphate buffer (pH 6.4), v/v/v), delivered at a flow rate of 1.0 mL min −1 . UV detection was performed at 245 nm. The optimized method was thoroughly validated, demonstrating to be selective, when the chromatogram was recorded with a diode-array detector and peak purities were evaluated (>0.9995). The method is robust and linear (r 2 > 0.99) over the range 0.05-2.5% (5-250% with regards to the 1% specification limit for both process-related impurities); it is also precise, regarding repeatability (RSD ≤ 1.5% for all of the analytes) and intermediate precision aspects and LOQ values for the impurities are below 0.01%. Method accuracy, evidenced by low bias of the results and analyte recoveries in the range of 99.1-102.7%, was assessed at five analyte concentration levels. The usefulness of the determination was also demonstrated through the analysis of different lots of pridinol mesylate bulk substance. The results indicate that the method is suitable for the quality control of the bulk manufacturing of pridinol mesylate drug substance.
Analytical and Bioanalytical Chemistry, 2005
A new, repeatable, and rapid method has been developed for resolution of binary mixtures of aceta... more A new, repeatable, and rapid method has been developed for resolution of binary mixtures of acetaminophen and diclofenac with minimum sample pretreatment and without separation of the analytes. The method, based on the PLS1 processing of absorbance data in the UV region, was successfully used for quantification of the drug content of three tablet preparations. The results obtained were in good agreement with HPLC recovery data. The method also enabled determination of drug-dissolution profiles of these commercial tablets, by simultaneous determination of both analytes during the dissolution test.
The stability of pridinol mesylate (PRI) was investigated under different stress conditions, incl... more The stability of pridinol mesylate (PRI) was investigated under different stress conditions, including hydrolytic, oxidative, photolytic and thermal, as recommended by the ICH guidelines. Relevant degradation was found to take place under acidic (0.1N HCl) and photolytic (visible and long-wavelength UV-light) conditions, both yielding the product resulting from water elimination (ELI), while submission to an oxidizing environment gave the N-oxidation derivative (NOX). The standards of these degradation products were synthesized and characterized by IR, 1 H and 13 C NMR spectroscopy. A simple, sensitive and specific HPLC method was developed for the quantification of PRI, ELI and NOX in bulk drug, and the conditions were optimized by means of a statistical design strategy. The separation employs a C 18 column and a 51:9:40 (v/v/v) mixture of MeOH, 2-propanol and potassium phosphate solution (50 mM, pH 6.0), as mobile phase, delivered at 1.0 ml min −1 ; the analytes were detected and quantified at 220 nm. The method was validated, demonstrating to be accurate and precise (repeatability and intermediate precision levels) within the corresponding linear ranges of PRI (0.1-1.5 mg ml −1 ; r = 0.9983, n = 18) and both impurities (0.1-1.3% relative to PRI, r = 0.9996 and 0.9995 for ELI and NOX, respectively, n = 18). Robustness against small modifications of pH and percentage of the aqueous mobile phase was ascertained and the limits of quantification of the analytes were also determined (0.4 and 0.5 g ml −1 ; 0.04% and 0.05% relative to PRI for ELI and NOX, respectively). Peak purity indices (>0.9997), obtained with the aid of diode-array detection, and satisfactory resolution (R s > 2.0) between PRI and its impurities established the specificity of the determination, all these results proving the stability-indicating capability of the method. The kinetics of the degradation of PRI in acid medium was also studied, determining that this is a first-order process with regards to drug concentration, with an activation energy of 25.5 Kcal mol −1 and a t 1/2 = 10,830 h, in 0.1N HCl at 38 • C.
Journal of Liquid Chromatography Amp Related Technologies, Nov 1, 2011
Journal of Liquid Chromatography Amp Related Technologies, 2012
Journal of Pharmaceutical and Biomedical Analysis
A simple and reliable reversed-phase high-perfomance liquid chromatographic method has been devel... more A simple and reliable reversed-phase high-perfomance liquid chromatographic method has been developed and validated for the simultaneous determination of meloxicam and pridinol mesylate in their synthetic mixtures and combined tablet formulations. Both drugs were separated on a 250mm×4.6mm C18 column packed with 5 �m particles. The mobile phase, optimized through an experimental design, was a 51:9:40 (v/v/v) mixture of methanol, isopropanol and 50mM potassium phosphate buffer (pH 5.9), pumped at a flow rate of 1.0 ml min−1. UV detection was performed at 225 nm. The method was validated in the sample concentration ranges of 33.7–61.8 mg l−1 for meloxicam and 8.8–16.8 mg l−1 for pridinol mesylate, where it demonstrated good linearity with r = 0.9989 and 0.9987 (n = 15), respectively. The assay was shown to be repeatable at concentration levels of 70%, 100% and 130%, with relative standard deviation values of 1.09% and 0.82% for meloxicam and pridinol, respectively. For independent 100...
International Journal of Pharmaceutics, 2009
A simple chemometric approach to differentiate among the three crystalline polymorphs of the mode... more A simple chemometric approach to differentiate among the three crystalline polymorphs of the model drug Furosemide (FUR) in a pharmaceutical dosage form is presented. The proposed method is based on the principal component analysis with confidence regions (PCA-CR) comparison of the dissolution profiles of the test pharmaceutical formulation, and formulations containing the different polymorphs, employed as the corresponding references.
Journal of Pharmaceutical and Biomedical Analysis, 2011
A photostability study of Valsartan (VAL) is reported. Exposure of the drug to UV-vis radiation (... more A photostability study of Valsartan (VAL) is reported. Exposure of the drug to UV-vis radiation ( > 320 nm) yielded two previously unknown compounds, which were detected by HPLC. Preparative amounts of the new potential degradation products (DP-1 and DP-2) were obtained by submitting VAL bulk drug to extensive photodegradation. The impurities were isolated by preparative normal phase column chromatography. Analytical information from the infrared, nuclear magnetic resonance and mass spectral data of the degradation products revealed their structures as N-[2 -(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-N-isobutylpentanamide (DP-1) and N-(diazirino[1,3f]phenanthridin-4-ylmethyl)-N-isobutylpentanamide (DP-2). DP-1 arose from decarboxylation of VAL, while DP-2 results from further loss of nitrogen from the tetrazole motif of DP-1, with concomitant cyclization to yield a tetracyclic diazacyclopropene derivative.
Journal of Pharmaceutical and Biomedical Analysis, 2008
The stability of pridinol mesylate (PRI) was investigated under different stress conditions, incl... more The stability of pridinol mesylate (PRI) was investigated under different stress conditions, including hydrolytic, oxidative, photolytic and thermal, as recommended by the ICH guidelines. Relevant degradation was found to take place under acidic (0.1N HCl) and photolytic (visible and long-wavelength UV-light) conditions, both yielding the product resulting from water elimination (ELI), while submission to an oxidizing environment gave the N-oxidation derivative (NOX). The standards of these degradation products were synthesized and characterized by IR, 1 H and 13 C NMR spectroscopy. A simple, sensitive and specific HPLC method was developed for the quantification of PRI, ELI and NOX in bulk drug, and the conditions were optimized by means of a statistical design strategy. The separation employs a C 18 column and a 51:9:40 (v/v/v) mixture of MeOH, 2-propanol and potassium phosphate solution (50 mM, pH 6.0), as mobile phase, delivered at 1.0 ml min −1 ; the analytes were detected and quantified at 220 nm. The method was validated, demonstrating to be accurate and precise (repeatability and intermediate precision levels) within the corresponding linear ranges of PRI (0.1-1.5 mg ml −1 ; r = 0.9983, n = 18) and both impurities (0.1-1.3% relative to PRI, r = 0.9996 and 0.9995 for ELI and NOX, respectively, n = 18). Robustness against small modifications of pH and percentage of the aqueous mobile phase was ascertained and the limits of quantification of the analytes were also determined (0.4 and 0.5 g ml −1 ; 0.04% and 0.05% relative to PRI for ELI and NOX, respectively). Peak purity indices (>0.9997), obtained with the aid of diode-array detection, and satisfactory resolution (R s > 2.0) between PRI and its impurities established the specificity of the determination, all these results proving the stability-indicating capability of the method. The kinetics of the degradation of PRI in acid medium was also studied, determining that this is a first-order process with regards to drug concentration, with an activation energy of 25.5 Kcal mol −1 and a t 1/2 = 10,830 h, in 0.1N HCl at 38 • C.
Journal of Pharmaceutical and Biomedical Analysis, 2001
A numerical method, based on the use of spectrophotometric data coupled to PLS-1 multivariate cal... more A numerical method, based on the use of spectrophotometric data coupled to PLS-1 multivariate calibration, is reported for the simultaneous determination of furosemide and amiloride hydrochloride in synthetic samples and commercial tablets. The method was applied in the concentration ranges of 8.0-13.0 mg l − 1 for furosemide and 1.0-1.6 mg l − 1 for amiloride hydrochloride. Its accuracy and precision were determined, and it was validated by the analysis of synthetic mixtures of both drugs. The method was successfully applied to the quantitation of furosemide and amiloride hydrochloride in three different pharmaceutical formulations, providing results in agreement with those obtained by HPLC. It allowed the rapid, accurate and precise simultaneous estimation of the concentration of both analytes of interest in spite of their important spectral overlap, high concentration relationship and the presence of small amounts of different, unmodelled, absorbing excipients.
Journal of Pharmaceutical and Biomedical Analysis, 2007
An alternative method for the determination of fexofenadine (FEX) and pseudoephedrine (PSE) in th... more An alternative method for the determination of fexofenadine (FEX) and pseudoephedrine (PSE) in their combined tablet formulation has been developed, employing the partial least squares (PLS) analysis of spectral data of the analytes in their pharmaceutical association. A full-factorially designed set of 16 synthetic samples was employed for calibration purposes. The calibration models were constructed with wavelengths selection, in the ultraviolet region, according to their predictive ability. These were validated internally by the leave-one-out procedure and externally, employing appropriate sets of validation samples. The described method was linear for both analytes, over the range 160.6-301.2 mg L −1 for FEX (R 2 = 0.9993) and between 325.6 and 610.5 mg L −1 for PSE (R 2 = 0.9992). It was accurate, exhibiting 99.8% and 99.9% drug recoveries for FEX and PSE, respectively (N = 9), while in the intermediate precision experiment relative standard deviations were 1.4% for FEX and 1.2% for PSE.
Journal of Pharmaceutical and Biomedical Analysis, 2002
The use of multivariate spectrophotometric calibration for the simultaneous analysis of synthetic... more The use of multivariate spectrophotometric calibration for the simultaneous analysis of synthetic samples and commercial tablet preparations containing hydrochlorothiazide (HCT) and amiloride hydrochloride (AMH) is reported. Partial least squares (PLS-1) analysis of electronic absorption spectral data allowed the rapid and accurate resolution of mixtures in which the analyte ratios were approximately 10:1, without the need of a previous separation step and without interference from other sample constituents. The method, validated by the analysis of synthetic mixtures of both drugs, where accuracy over the linear working range as well as inter-and intra-assay precision were determined, was used in the concentration ranges of 21.7 Á/30.4 mg l (1 for HCT and 1.8 Á/3.0 mg l (1 for AMH. The proposed method was successfully applied to the evaluation of the stability of the stock solutions of the analytes in MeOH Á/H 2 O and to the elaboration of drug dissolution profiles of commercial tablets, results being concordant with those furnished by the USP technique. The method was also employed for the determination of drug content in two different pharmaceutical formulations, providing results that were in excellent agreement with those obtained by HPLC. #
Journal of Pharmaceutical and Biomedical Analysis, 2004
Different chemometric methods such as classical least squares (CLS), principal components regress... more 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, 0 D-PLS-1, 1 D-PCR and 1 D-PLS-1 were reproducible and gave statistically similar results, while 0 D-CLS and 1 D-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. .ar (T.S. Kaufman).
Journal of Liquid Chromatography & Related Technologies, 2010
Journal of Liquid Chromatography & Related Technologies, 2012
European Journal of Pharmaceutical Sciences, 2008
Acetaminophen Furosemide Multivariate method a b s t r a c t A new approach for testing batch "si... more Acetaminophen Furosemide Multivariate method a b s t r a c t A new approach for testing batch "similarity" through comparison of drug dissolution profiles, based on principal component analysis with the establishment of a confidence region (PCA-CR), is presented. The dissolution curves corresponding to three brands each of Furosemide and Acetaminophen tablets, taken as model drugs, were prepared by dissolution measurements at multiple pre-specified time points. Reference and test data were simultaneously subjected to PCA and pairwise comparisons between the dissolution characteristics of lots of the same and different brands were carried out. The comparisons involved plotting the weighed scores of the first two principal components of reference and test lots, while decision about "similarity" was made by checking for inclusion of more than 80% of the tablets of the test lot in the 95% confidence ellipse of the reference samples. Two published datasets were also analyzed in the same fashion and all the results were compared with information provided by the difference (f 1 ) and similarity (f 2 ) factor tests. Unlike the f 2 criterion, the proposed method reflects variability within the individual dissolution curves, being also highly sensitive to profile (shape and size) variations. Comparison between the area enclosed by the confidence ellipses of the weighed scores plot and the region obtained from the bootstrap-calculated acceptable values of the corresponding f 2 tests suggested that PCA-CR represents, in general, a more discriminating standard.
Bioorganic & Medicinal Chemistry Letters, 2006
Six 3H-spiro[benzofuran-2,1 0 -cyclohexane] derivatives were synthesized from naturally occurring... more Six 3H-spiro[benzofuran-2,1 0 -cyclohexane] derivatives were synthesized from naturally occurring filifolinol, and their classical complement pathway inhibitory activity was determined. IC 50 values of the most potent compounds were comparable to the activity of the natural complement inhibitor K76-COOH and some synthetic tricyclic analogs of it.
Analytical and Bioanalytical Chemistry, 2008
A convenient new method for the simultaneous determination of losartan potassium and hydrochlorot... more A convenient new method for the simultaneous determination of losartan potassium and hydrochlorothiazide, with minimum sample pretreatment, is described. The procedure, based on the multivariate analysis of spectral data in the 220−274 nm region by the partial least squares algorithm, is linear in the concentration range 1.06− 5.70 mg L −1 for hydrochlorothiazide and 4.0−22.2 mg L −1 for losartan. It is simple, rapid and robust, allowing accurate and precise results, with drug recovery rates of 99.3 and 100.4% and relative standard deviations of 1.7 and 1.0% obtained for hydrochlorothiazide and losartan, respectively. The method was applied to the simultaneous determination of both analytes in tablets, and it provided good results which were in statistical agreement with those provided by independent HPLC analyses of the samples. The method has also been successfully applied for the construction of drug dissolution profiles of a commercial pharmaceutical preparation containing both analytes.
Analytical and Bioanalytical Chemistry, 2003
A new, repeatable, and rapid method has been developed for resolution of binary mixtures of aceta... more A new, repeatable, and rapid method has been developed for resolution of binary mixtures of acetaminophen and diclofenac with minimum sample pretreatment and without separation of the analytes. The method, based on the PLS1 processing of absorbance data in the UV region, was successfully used for quantification of the drug content of three tablet preparations. The results obtained were in good agreement with HPLC recovery data. The method also enabled determination of drug-dissolution profiles of these commercial tablets, by simultaneous determination of both analytes during the dissolution test.
Analytical and Bioanalytical Chemistry, 2006
Two new analytical methods have been developed as convenient and useful alternatives for simultan... more Two new analytical methods have been developed as convenient and useful alternatives for simultaneous determination of hydrochlorothiazide (HCT) and propranolol hydrochloride (PRO) in pharmaceutical formulations. The methods are based on the first derivative of ratio spectra (DRS) and on partial least squares (PLS) analysis of the ultraviolet absorption spectra of the samples in the 250-350-nm region. The methods were calibrated between 8.7 and 16.0 mg L −1 for HCT and between 14.0 and 51.5 mg L −1 for PRO. An asymmetric full-factorial design and wavelength selection (277-294 nm for HCT and 297-319 for PRO) were used for the PLS method and signal intensities at 276 and 322 nm were used in the DRS method for HCT and PRO, respectively. Performance characteristics of the analytical methods were evaluated by use of validation samples and both methods showed to be accurate and precise, furnishing near quantitative analyte recoveries (100.4 and 99.3% for HCT and PRO by use of PLS) and relative standard deviations below 2%. For PLS the lower limits of quantification were 0.37 and 0.66 mg L −1 for HCT and PRO, respectively, whereas for DRS they were 1.15 and 3.05 mg L −1 for HCT and PRO, respectively. The methods were used for quantification of HCT and PRO in synthetic mixtures and in two commercial tablet preparations containing different proportions of the analytes. The results of the drug content assay and the tablet dissolution test were in statistical agreement (p<0.05) with those furnished by the official procedures of the USP 29. Preparation of dissolution profiles of the combined tablet formulations was also performed with the aid of the proposed methods. The methods are easy to apply, use relatively simple equipment, require minimum sample pre-treatment, enable high sample throughput, and generate less solvent waste than other procedures.
Analytica Chimica Acta, 2009
A simple high performance liquid chromatographic method for the determination of process-related ... more A simple high performance liquid chromatographic method for the determination of process-related impurities in bulk drug of the central anticholinergic compound pridinol mesylate, has been developed and validated. Spectroscopically characterized synthetic impurities were used as standards. The chromatographic separation was optimized employing an experimental design strategy, and was achieved on a C 18 column with a mobile phase containing 50 mM potassium phosphate buffer (pH 6.4), v/v/v), delivered at a flow rate of 1.0 mL min −1 . UV detection was performed at 245 nm. The optimized method was thoroughly validated, demonstrating to be selective, when the chromatogram was recorded with a diode-array detector and peak purities were evaluated (>0.9995). The method is robust and linear (r 2 > 0.99) over the range 0.05-2.5% (5-250% with regards to the 1% specification limit for both process-related impurities); it is also precise, regarding repeatability (RSD ≤ 1.5% for all of the analytes) and intermediate precision aspects and LOQ values for the impurities are below 0.01%. Method accuracy, evidenced by low bias of the results and analyte recoveries in the range of 99.1-102.7%, was assessed at five analyte concentration levels. The usefulness of the determination was also demonstrated through the analysis of different lots of pridinol mesylate bulk substance. The results indicate that the method is suitable for the quality control of the bulk manufacturing of pridinol mesylate drug substance.
Analytical and Bioanalytical Chemistry, 2005
A new, repeatable, and rapid method has been developed for resolution of binary mixtures of aceta... more A new, repeatable, and rapid method has been developed for resolution of binary mixtures of acetaminophen and diclofenac with minimum sample pretreatment and without separation of the analytes. The method, based on the PLS1 processing of absorbance data in the UV region, was successfully used for quantification of the drug content of three tablet preparations. The results obtained were in good agreement with HPLC recovery data. The method also enabled determination of drug-dissolution profiles of these commercial tablets, by simultaneous determination of both analytes during the dissolution test.