In recent years, near-infrared (NIR) spectroscopy has gained wide acceptance in different fields ... more In recent years, near-infrared (NIR) spectroscopy has gained wide acceptance in different fields by virtue of its advantages over other analytical techniques, the most salient of which is its ability to record spectra for solid and liquid samples with no prior manipulation. Also, developments in instrumentation have resulted in the manufacture of spectrophotometers capable of quickly providing spectra that are flexible enough for use in different situations; thus, portable equipment can record spectra on site or even at production lines. This article discusses the features of NIR spectroscopy that have driven forward its dramatic development in a wide range of analytical fields in the last few years. #
Obtaining completely uniform distribution of the active principle and excipients in a pharmaceuti... more Obtaining completely uniform distribution of the active principle and excipients in a pharmaceutical preparation is essential with a view to ensuring correct dosage. Uniformity in pharmaceutical formulations has usually been controlled by collecting samples at different stages of the process in order to determine the active principle using a chromatographic or UV-Visible spectroscopic method. In this work, near infrared reflectance spectroscopy (NIRS) was used to monitor blending in order to ensure uniformity in a mixture consisting of three typical pharmaceutical excipients and one active principle. To this end, a method for calculating the Mean Square of Differences between two consecutive spectra was developed with a view to expeditiously identifying the time mixture homogeneity was attained. The performance of the proposed method was compared with that of two others routinely employed to monitor blending by use of the NIRS technique and the results were found to be quite consistent.
The difficulties of comparing results in medical attention of out-of-hospital cardiac arrest (OOH... more The difficulties of comparing results in medical attention of out-of-hospital cardiac arrest (OOHCA) patients are well known. Apart from methodological differences, the structure of out-of-hospital emergency services (EMS) can contribute to this. We describe the main features of EMS in Spain.
A new method for the characterization and determination of crystalline miokamycin in a pharmaceut... more A new method for the characterization and determination of crystalline miokamycin in a pharmaceutical preparation using near infrared spectroscopy is proposed. The procedure involves the identification against a spectral library of samples with contents above the legal limit (viz. 5% of the crystalline form in amorphous miokamycin) using the Mahalanobis distance as the discriminating criterion, and the determination of the total and crystalline contents using partial least squares models that provide errors <1%. The proposed method was validated following the ICH guidelines. Its simplicity and expeditiousness make it highly suitable for quality control analyses of solid dosage forms. ß
ABSTRACT The US Food and Drug Administration&#39;s process analytical technology (PAT) initia... more ABSTRACT The US Food and Drug Administration&#39;s process analytical technology (PAT) initiative has encouraged the pharmaceutical industry to strengthen research with a view to developing new analytical technologies for improving blending processes. Near infrared (NIR) spectroscopy, which is sensitive to both physical and chemical attributes of substances, has proved a powerful non-invasive analytical technique for this purpose. In this paper, we propose a criterion to assess blending uniformity and accurately detect the end-point of a blending process. The criterion was established by using partial least squares (PLS) regression and calibration-free methods including moving block standard deviation of spectra, principal component scores distance analysis and the mixing index (M). The mixing index was found to provide accurate, robust results with a view to assessing blending uniformity, as was PLS for detecting blending end-points. This novel criterion allowed us to assess the homogeneity of a mixture, without the need of a reference method, a golden batch or a calibration set. In fact, the M index was found to be an easy method and it is a highly suitable tool for PAT as it allows the accurate, precise real-time monitoring of blending processes with minimal intervention of the analyst.
ABSTRACT Although miniaturisation of vibrational spectrometers began approximately a decade ago, ... more ABSTRACT Although miniaturisation of vibrational spectrometers began approximately a decade ago, only within the last couple of years have real hand-held Raman, infrared and near infrared (NIR) scanning spectrometers became commercially available. On the customer end the development of portable instrumentation was driven by the request for more flexibility of on-site measurements and on the manufacturer side it was supported by the potential and advantages of micro-electromechanical systems (MEMS) production and the implementation of new technologies. With reference to NIR spectroscopy the expectations for a real hand-held system (&lt;100g) have been recently realised by a pocket-sized spectrometer with a linear variable filter technology (LVF) as monochromator principle and the additional benefit of significantly reduced costs compared to other portable systems. For a real breakthrough and impact of this instrument, however, it had to be demonstrated that competitive analytical results can be achieved. In this respect, the present communication has put to test the performance of this micro-NIR system with reference to selected qualitative and quantitative pharmaceutical applications.
Chemometrics and Intelligent Laboratory Systems, 1999
. The relationship between absorption in the near-infrared NIR spectral region and the target ana... more . The relationship between absorption in the near-infrared NIR spectral region and the target analytical parameter is frequently of the non-linear type. The origin of the non-linearity can be widely varied and difficult to identify. In some cases, the relationship between absorption and the analytical parameter of interest is intrinsically non-linear owing to the very chemical nature of the sample or analyte concerned. In this work, various multivariate calibration procedures were tested with a view to overcoming intrinsic non-linearity in NIR reflectance. An approach to solving the problem is suggested. Calibration was done, after transformation of spectra, by using linear and non-linear techniques. The linear calibration techniques Ž . Ž . Ž . used are partial least squares PLS regression with and without variable selection , linear PLS with X projection LP-PLS Ž . and stepwise polynomial principal component SWP-PC regression. Non-linear calibration methods included polynomial PLS Ž . Ž . PPLS and artificial neural networks ANNs . Results were compared on the basis of NIR spectra for ampicillin trihydrate samples, where the simultaneous presence of crystallization water and surface moisture gives rise to intrinsic non-linearity that affects the determination of the total water content in the sample. The best results were obtained by using the non-linear calibration techniques. q
Near-infrared (NIR) spectroscopy is proposed for the in-line quantitative and kinetic study of th... more Near-infrared (NIR) spectroscopy is proposed for the in-line quantitative and kinetic study of the polymerization of epsilon-caprolactone and eventually to facilitate real-time control of the manufacturing process. Spectra were acquired with a fibre-optic probe operating in transflectance mode immersed in the reactor. The NIR data acquired were processed using a multivariate curve resolution alternating least squares (MCR-ALS) algorithm. The proposed method allows calculation of the concentration and spectral profiles of the species involved in the reaction. The key point of this method is the lack of reference concentrations needed to perform the MCR-ALS method. The use of an extended spectral matrix using both process and pure analyte spectra solves the rank deficiency. The concentration profiles obtained were used to calculate a kinetic fitting of the reaction, but the method was improved by applying kinetic constraints (hard modelling). The rate constants of batches at different temperatures and the energy of activation for this reaction were calculated. Whenever possible, the hard modelling combined with the MCR-ALS method improves the fit of the experimental data: the results show good correlation between the NIR and reference data and allow the collection of high-quality kinetic information on the reaction (rate constants and energy of activation).
... Rafael Beneyto Development and Quality Assurance Department, ICI Spain SA (Mevisa Site), Barc... more ... Rafael Beneyto Development and Quality Assurance Department, ICI Spain SA (Mevisa Site), Barcelona, Spain Marta Porcel Department of Chemistry, Faculty of Sciences, Autonomous University of Barcelona, Barcelona, Spain ...
Analytical and Bioanalytical Chemistry, Feb 1, 2003
A simple, fast capillary electrophoresis method for determining the total ketoprofen content in a... more A simple, fast capillary electrophoresis method for determining the total ketoprofen content in an oral pharmaceutical formulation is proposed. The addition of 75 mM of heptakis(tri-O-methyl)-β-cyclodextrin to the background electrolyte allows the quantitation of the enantiomeric impurity of (R)-(-)-ketoprofen contained in the formulation. A relative limit of detection is proposed as a measure of the lowest detectable enantiomeric impurity and the results show that the method can detect the minor enantiomer at levels as low as 0.04% in (S)-(+)-ketoprofen. The chiral method was validated following ICH recommendations and the quality parameters obtained show the suitability of the proposed method. The analysis of samples examined during the course of a stability study under chiral and achiral conditions revealed that the total ketoprofen content did not change significantly with time and the enantiomeric impurity range was 0.1-0.4%.
Environmental Toxicology and Chemistry Setac, Sep 30, 2001
The E, E-(4,4Ј-bis[2-sulfostyryl]biphenyl) (DSBP) is a fluorescent whitening agent widely used by... more The E, E-(4,4Ј-bis[2-sulfostyryl]biphenyl) (DSBP) is a fluorescent whitening agent widely used by the textile and detergent industries to whiten fabrics. Hypochlorite used to bleach fabrics oxidizes DSBP slowly at room temperature and in a higher rate at 60ЊC. The ions of metals such as Fe, Cu, and Mn accelerate the process considerably. At ambient temperature, the oxidation results from cleavage of the stilbene bonds and involves the formation of various intermediates that evolve to end products. The intermediates form within minutes to hours and the end products within months. At 60ЊC or in presence of the previously mentioned transition metals, intermediates form within minutes and the end products within days. The end products of the oxidation are 4sulfobenzaldehyde and 4,4Ј-bisaldehyde biphenyl; in the presence of excess of hypochlorite, however, the process yields their corresponding oxidized derivatives 4-sulfobenzoic acid and 4,4Ј-biphenyldicarboxylic acid. Despite the chlorinating ability of hypochlorite, the major degradation products formed contain no chlorine.
The accelerated transformation of three azithromycin pseudo-polymorphs (viz. the anhydrous, monoh... more The accelerated transformation of three azithromycin pseudo-polymorphs (viz. the anhydrous, monohydrate (MH), and dihydrate (DH) forms) at a high temperature and moisture level was examined by near infrared spectroscopy (NIRS). The most marked spectral differences between the pseudo-polymorphs occurred in the 1800-2200 nm region, which corresponds to the first overtone for water. The qualitative analysis of the NIR spectra for the pseudo-polymorphs following storage in a stove at 608C at 100% relative humidity for 60 days suggests that the crystalline forms (viz. the MH and DH) are stable, whereas the amorphous (anhydrous) form evolves to the DH. This was confirmed by determining the amounts of water and DH present in anhydrous azithromycin and the MH by use of partial least-squares regression (PLSR). The method used to quantify the DH in MH samples was developed and validated in accordance with the standards of the International Conference of Harmonization (ICH) and the European Medicines Agency (EMEA) with a view to its subsequent application by the pharmaceutical industry. The limits of detection (LD) and quantitation (LQ) for the DH in MH provided by the NIRS method were consistent with those obtained by X-ray diffraction (XRD) methodology. This testifies to the accuracy of the proposed method.
Analytical and Bioanalytical Chemistry, Sep 3, 2007
Cosmetic preparations typically consist of mixtures of various compounds of natural origin or the... more Cosmetic preparations typically consist of mixtures of various compounds of natural origin or their derivatives. Their analysis is made rather difficult by their usually high complexity and is utterly impossible with a single analytical method; also, there is usually little to be gained by determining every individual component of the mixture. Rather, analyses are aimed at ensuring a proper balance between the contents of each component and thus require the use of methods capable of delivering global information. The combined use of near-infrared (NIR) spectroscopy and multivariate spectral processing chemometric techniques has enabled the development of effective methods for establishing the composition of complex samples with acceptable levels of analytical properties, such as accuracy, precision and throughput. In this work, we developed partial least squares calibration models for the determination of each component in a cosmetic mixture, and global indices (viz. the hydroxyl value), simply from the NIR spectrum of the sample. The models thus obtained are accurate enough for use in quality control analyses of cosmetic preparations and provide an effective alternative to existing conventional global methods.
Analytical and Bioanalytical Chemistry, Jan 3, 2007
Industrial mortars consist primarily of a mixture of cement and an aggregate plus a small amount ... more Industrial mortars consist primarily of a mixture of cement and an aggregate plus a small amount of additives that are used to modify specific properties. Using too high or too low additive rates usually results in the loss of desirable properties in the end product. This entails carefully controlling the amounts of additives added to mortar in order to ensure correct dosing and/or adequate homogeneity in the final mixture. Near-IR (NIR) spectroscopy has proved effective for this purpose as it requires no sample pretreatment and affords expeditious analyses. The purpose of this work was to determine two organic additives (viz. Ad1 and Ad2) in mortars by using partial least squares regression multivariate calibration models constructed from NIR spectroscopic data. The additives are used to expedite setting and increase cohesion between particles in the mortar. In order to ensure that the sample set contained natural variability in the samples, we used a methodology based on experimental design to construct a representative set of samples. This novel design is based on a hexagonal antiprism that encompasses the concentration ranges spanned by the analytes and the variability inherent in each additive. The D-optimality criterion was used to obtain various combinations between Ad1 and Ad2 additive classes. The partial least squares calibration models thus constructed for each additive provided accurate predictions: the intercept and the slope of the plots of predicted values versus reference values for each additive were close to 0 and 1, respectively, and their confidence ranges included the respective value. The ensuing analytical methods were validated by using an external sample set.
A simple, fast capillary electrophoresis method for determining the total ketoprofen content in a... more A simple, fast capillary electrophoresis method for determining the total ketoprofen content in an oral pharmaceutical formulation is proposed. The addition of 75 mM of heptakis(tri- O-methyl)-beta-cyclodextrin to the background electrolyte allows the quantitation of the enantiomeric impurity of ( R)-(-)-ketoprofen contained in the formulation. A relative limit of detection is proposed as a measure of the lowest detectable enantiomeric impurity and the results show that the method can detect the minor enantiomer at levels as low as 0.04% in ( S)-(+)-ketoprofen. The chiral method was validated following ICH recommendations and the quality parameters obtained show the suitability of the proposed method. The analysis of samples examined during the course of a stability study under chiral and achiral conditions revealed that the total ketoprofen content did not change significantly with time and the enantiomeric impurity range was 0.1-0.4%.
Journal of chromatography. B, Biomedical sciences and applications, Jan 5, 2001
Pharmaceutical preparations usually contain preservatives and sweeteners. When parabens are used ... more Pharmaceutical preparations usually contain preservatives and sweeteners. When parabens are used as preservatives and a polyol as a sweetener, a transesterification reaction may happen, yielding the transester polyol-paraben. The products formed in the transesterification reaction of methylparaben and sorbitol were analyzed by micellar electrokinetic chromatography and by HPLC. Up to six positional isomers of sorbitolparaben (SPB) can be produced. However, only three peaks were found by HPLC. The higher efficiency and resolution power of MEKC allowed one to resolve five peaks. Results were compared with those obtained by capillary zone electrophoresis in borate buffer, where the separation of isomers occurred in a different way, because of a complexation between SPB and borate.
The growing interest of the pharmaceutical industry in Near Infrared-Chemical Imaging (NIR-CI) is... more The growing interest of the pharmaceutical industry in Near Infrared-Chemical Imaging (NIR-CI) is a result of its high usefulness for quality control analyses of drugs throughout their production process (particularly of its non-destructive nature and expeditious data acquisition). In this work, the concentration and distribution of the major and minor components of pharmaceutical tablets are determined and the spatial distribution from the internal and external sides has been obtained. In addition, the same NIR-CI allowed the coating thickness and its surface distribution to be quantified. Images were processed to extract the target data and calibration models constructed using the Partial Least Squares (PLS) algorithms. The concentrations of Active Pharmaceutical Ingredient (API) and excipients obtained for uncoated cores were essentially identical to the nominal values of the pharmaceutical formulation. But the predictive ability of the calibration models applied to the coated tablets decreased as the coating thickness increased.
ABSTRACT Near-infrared (NIR) is a spectroscopic method based on the absorption of light in the wa... more ABSTRACT Near-infrared (NIR) is a spectroscopic method based on the absorption of light in the wavelength region between 700 and 2500 nm due to vibrations of molecular functional groups in the sample. These spectral features arise from overtones and combinations of the fundamental molecular vibrations of these groups that occur in the infrared (IR) at longer wavelengths. NIR is rich with features arising predominantly from vibrations of C–H, O–H, and N–H.(1) NIR spectra are acquired by determining the absorbance, A, of light over a continuous range of wavelengths in spectrophotometers or at several specific wavelengths in fixed-filter photometers. Absorbance is defined by the following equation: (1) where I is the signal intensity from the sample relative to the signal intensity from a reference, I0. The reference can be an empty transmission sample cell for liquids, or it can be a broadband spectral reflector, such as a white ceramic, for reflectance measurements of solids. Absorbance is usually linearly related to concentration, following Beer&#39;s Law (Equation 2): (2) where epsiv represents the molar extinction coefficient, C is the concentration of the species, and l is the optical pathlength of light through the sample. For a particular species and fixed experimental setup, epsiv and l are constants. Letting a constant, k = (epsivl)–1, then (Equation 3) (3) A principal advantage of NIR over mid-IR for process applications is the ability to use fiber optics to transmit light between the instrument and the sample over considerable distance with NIR. This permits the instrument, a potential source of ignition, to be placed in safe areas where flammable vapors exist. Only the fiber-optic probe in contact with the sample and the optical fibers that connect to the instrument need be placed in the hazardous location. A disadvantage of NIR is the characteristics of the spectra, which are typically composed of broad, overlapping peaks in comparison to IR spectra. This often requires the use of sophisticated data analysis methods that place additional demands on vendors to provide stable NIR instruments and upon manufacturers and end-users to have highly trained staff, often at the PhD level, for calibration model development, implementation, and maintenance.
In recent years, near-infrared (NIR) spectroscopy has gained wide acceptance in different fields ... more In recent years, near-infrared (NIR) spectroscopy has gained wide acceptance in different fields by virtue of its advantages over other analytical techniques, the most salient of which is its ability to record spectra for solid and liquid samples with no prior manipulation. Also, developments in instrumentation have resulted in the manufacture of spectrophotometers capable of quickly providing spectra that are flexible enough for use in different situations; thus, portable equipment can record spectra on site or even at production lines. This article discusses the features of NIR spectroscopy that have driven forward its dramatic development in a wide range of analytical fields in the last few years. #
Obtaining completely uniform distribution of the active principle and excipients in a pharmaceuti... more Obtaining completely uniform distribution of the active principle and excipients in a pharmaceutical preparation is essential with a view to ensuring correct dosage. Uniformity in pharmaceutical formulations has usually been controlled by collecting samples at different stages of the process in order to determine the active principle using a chromatographic or UV-Visible spectroscopic method. In this work, near infrared reflectance spectroscopy (NIRS) was used to monitor blending in order to ensure uniformity in a mixture consisting of three typical pharmaceutical excipients and one active principle. To this end, a method for calculating the Mean Square of Differences between two consecutive spectra was developed with a view to expeditiously identifying the time mixture homogeneity was attained. The performance of the proposed method was compared with that of two others routinely employed to monitor blending by use of the NIRS technique and the results were found to be quite consistent.
The difficulties of comparing results in medical attention of out-of-hospital cardiac arrest (OOH... more The difficulties of comparing results in medical attention of out-of-hospital cardiac arrest (OOHCA) patients are well known. Apart from methodological differences, the structure of out-of-hospital emergency services (EMS) can contribute to this. We describe the main features of EMS in Spain.
A new method for the characterization and determination of crystalline miokamycin in a pharmaceut... more A new method for the characterization and determination of crystalline miokamycin in a pharmaceutical preparation using near infrared spectroscopy is proposed. The procedure involves the identification against a spectral library of samples with contents above the legal limit (viz. 5% of the crystalline form in amorphous miokamycin) using the Mahalanobis distance as the discriminating criterion, and the determination of the total and crystalline contents using partial least squares models that provide errors <1%. The proposed method was validated following the ICH guidelines. Its simplicity and expeditiousness make it highly suitable for quality control analyses of solid dosage forms. ß
ABSTRACT The US Food and Drug Administration&#39;s process analytical technology (PAT) initia... more ABSTRACT The US Food and Drug Administration&#39;s process analytical technology (PAT) initiative has encouraged the pharmaceutical industry to strengthen research with a view to developing new analytical technologies for improving blending processes. Near infrared (NIR) spectroscopy, which is sensitive to both physical and chemical attributes of substances, has proved a powerful non-invasive analytical technique for this purpose. In this paper, we propose a criterion to assess blending uniformity and accurately detect the end-point of a blending process. The criterion was established by using partial least squares (PLS) regression and calibration-free methods including moving block standard deviation of spectra, principal component scores distance analysis and the mixing index (M). The mixing index was found to provide accurate, robust results with a view to assessing blending uniformity, as was PLS for detecting blending end-points. This novel criterion allowed us to assess the homogeneity of a mixture, without the need of a reference method, a golden batch or a calibration set. In fact, the M index was found to be an easy method and it is a highly suitable tool for PAT as it allows the accurate, precise real-time monitoring of blending processes with minimal intervention of the analyst.
ABSTRACT Although miniaturisation of vibrational spectrometers began approximately a decade ago, ... more ABSTRACT Although miniaturisation of vibrational spectrometers began approximately a decade ago, only within the last couple of years have real hand-held Raman, infrared and near infrared (NIR) scanning spectrometers became commercially available. On the customer end the development of portable instrumentation was driven by the request for more flexibility of on-site measurements and on the manufacturer side it was supported by the potential and advantages of micro-electromechanical systems (MEMS) production and the implementation of new technologies. With reference to NIR spectroscopy the expectations for a real hand-held system (&lt;100g) have been recently realised by a pocket-sized spectrometer with a linear variable filter technology (LVF) as monochromator principle and the additional benefit of significantly reduced costs compared to other portable systems. For a real breakthrough and impact of this instrument, however, it had to be demonstrated that competitive analytical results can be achieved. In this respect, the present communication has put to test the performance of this micro-NIR system with reference to selected qualitative and quantitative pharmaceutical applications.
Chemometrics and Intelligent Laboratory Systems, 1999
. The relationship between absorption in the near-infrared NIR spectral region and the target ana... more . The relationship between absorption in the near-infrared NIR spectral region and the target analytical parameter is frequently of the non-linear type. The origin of the non-linearity can be widely varied and difficult to identify. In some cases, the relationship between absorption and the analytical parameter of interest is intrinsically non-linear owing to the very chemical nature of the sample or analyte concerned. In this work, various multivariate calibration procedures were tested with a view to overcoming intrinsic non-linearity in NIR reflectance. An approach to solving the problem is suggested. Calibration was done, after transformation of spectra, by using linear and non-linear techniques. The linear calibration techniques Ž . Ž . Ž . used are partial least squares PLS regression with and without variable selection , linear PLS with X projection LP-PLS Ž . and stepwise polynomial principal component SWP-PC regression. Non-linear calibration methods included polynomial PLS Ž . Ž . PPLS and artificial neural networks ANNs . Results were compared on the basis of NIR spectra for ampicillin trihydrate samples, where the simultaneous presence of crystallization water and surface moisture gives rise to intrinsic non-linearity that affects the determination of the total water content in the sample. The best results were obtained by using the non-linear calibration techniques. q
Near-infrared (NIR) spectroscopy is proposed for the in-line quantitative and kinetic study of th... more Near-infrared (NIR) spectroscopy is proposed for the in-line quantitative and kinetic study of the polymerization of epsilon-caprolactone and eventually to facilitate real-time control of the manufacturing process. Spectra were acquired with a fibre-optic probe operating in transflectance mode immersed in the reactor. The NIR data acquired were processed using a multivariate curve resolution alternating least squares (MCR-ALS) algorithm. The proposed method allows calculation of the concentration and spectral profiles of the species involved in the reaction. The key point of this method is the lack of reference concentrations needed to perform the MCR-ALS method. The use of an extended spectral matrix using both process and pure analyte spectra solves the rank deficiency. The concentration profiles obtained were used to calculate a kinetic fitting of the reaction, but the method was improved by applying kinetic constraints (hard modelling). The rate constants of batches at different temperatures and the energy of activation for this reaction were calculated. Whenever possible, the hard modelling combined with the MCR-ALS method improves the fit of the experimental data: the results show good correlation between the NIR and reference data and allow the collection of high-quality kinetic information on the reaction (rate constants and energy of activation).
... Rafael Beneyto Development and Quality Assurance Department, ICI Spain SA (Mevisa Site), Barc... more ... Rafael Beneyto Development and Quality Assurance Department, ICI Spain SA (Mevisa Site), Barcelona, Spain Marta Porcel Department of Chemistry, Faculty of Sciences, Autonomous University of Barcelona, Barcelona, Spain ...
Analytical and Bioanalytical Chemistry, Feb 1, 2003
A simple, fast capillary electrophoresis method for determining the total ketoprofen content in a... more A simple, fast capillary electrophoresis method for determining the total ketoprofen content in an oral pharmaceutical formulation is proposed. The addition of 75 mM of heptakis(tri-O-methyl)-β-cyclodextrin to the background electrolyte allows the quantitation of the enantiomeric impurity of (R)-(-)-ketoprofen contained in the formulation. A relative limit of detection is proposed as a measure of the lowest detectable enantiomeric impurity and the results show that the method can detect the minor enantiomer at levels as low as 0.04% in (S)-(+)-ketoprofen. The chiral method was validated following ICH recommendations and the quality parameters obtained show the suitability of the proposed method. The analysis of samples examined during the course of a stability study under chiral and achiral conditions revealed that the total ketoprofen content did not change significantly with time and the enantiomeric impurity range was 0.1-0.4%.
Environmental Toxicology and Chemistry Setac, Sep 30, 2001
The E, E-(4,4Ј-bis[2-sulfostyryl]biphenyl) (DSBP) is a fluorescent whitening agent widely used by... more The E, E-(4,4Ј-bis[2-sulfostyryl]biphenyl) (DSBP) is a fluorescent whitening agent widely used by the textile and detergent industries to whiten fabrics. Hypochlorite used to bleach fabrics oxidizes DSBP slowly at room temperature and in a higher rate at 60ЊC. The ions of metals such as Fe, Cu, and Mn accelerate the process considerably. At ambient temperature, the oxidation results from cleavage of the stilbene bonds and involves the formation of various intermediates that evolve to end products. The intermediates form within minutes to hours and the end products within months. At 60ЊC or in presence of the previously mentioned transition metals, intermediates form within minutes and the end products within days. The end products of the oxidation are 4sulfobenzaldehyde and 4,4Ј-bisaldehyde biphenyl; in the presence of excess of hypochlorite, however, the process yields their corresponding oxidized derivatives 4-sulfobenzoic acid and 4,4Ј-biphenyldicarboxylic acid. Despite the chlorinating ability of hypochlorite, the major degradation products formed contain no chlorine.
The accelerated transformation of three azithromycin pseudo-polymorphs (viz. the anhydrous, monoh... more The accelerated transformation of three azithromycin pseudo-polymorphs (viz. the anhydrous, monohydrate (MH), and dihydrate (DH) forms) at a high temperature and moisture level was examined by near infrared spectroscopy (NIRS). The most marked spectral differences between the pseudo-polymorphs occurred in the 1800-2200 nm region, which corresponds to the first overtone for water. The qualitative analysis of the NIR spectra for the pseudo-polymorphs following storage in a stove at 608C at 100% relative humidity for 60 days suggests that the crystalline forms (viz. the MH and DH) are stable, whereas the amorphous (anhydrous) form evolves to the DH. This was confirmed by determining the amounts of water and DH present in anhydrous azithromycin and the MH by use of partial least-squares regression (PLSR). The method used to quantify the DH in MH samples was developed and validated in accordance with the standards of the International Conference of Harmonization (ICH) and the European Medicines Agency (EMEA) with a view to its subsequent application by the pharmaceutical industry. The limits of detection (LD) and quantitation (LQ) for the DH in MH provided by the NIRS method were consistent with those obtained by X-ray diffraction (XRD) methodology. This testifies to the accuracy of the proposed method.
Analytical and Bioanalytical Chemistry, Sep 3, 2007
Cosmetic preparations typically consist of mixtures of various compounds of natural origin or the... more Cosmetic preparations typically consist of mixtures of various compounds of natural origin or their derivatives. Their analysis is made rather difficult by their usually high complexity and is utterly impossible with a single analytical method; also, there is usually little to be gained by determining every individual component of the mixture. Rather, analyses are aimed at ensuring a proper balance between the contents of each component and thus require the use of methods capable of delivering global information. The combined use of near-infrared (NIR) spectroscopy and multivariate spectral processing chemometric techniques has enabled the development of effective methods for establishing the composition of complex samples with acceptable levels of analytical properties, such as accuracy, precision and throughput. In this work, we developed partial least squares calibration models for the determination of each component in a cosmetic mixture, and global indices (viz. the hydroxyl value), simply from the NIR spectrum of the sample. The models thus obtained are accurate enough for use in quality control analyses of cosmetic preparations and provide an effective alternative to existing conventional global methods.
Analytical and Bioanalytical Chemistry, Jan 3, 2007
Industrial mortars consist primarily of a mixture of cement and an aggregate plus a small amount ... more Industrial mortars consist primarily of a mixture of cement and an aggregate plus a small amount of additives that are used to modify specific properties. Using too high or too low additive rates usually results in the loss of desirable properties in the end product. This entails carefully controlling the amounts of additives added to mortar in order to ensure correct dosing and/or adequate homogeneity in the final mixture. Near-IR (NIR) spectroscopy has proved effective for this purpose as it requires no sample pretreatment and affords expeditious analyses. The purpose of this work was to determine two organic additives (viz. Ad1 and Ad2) in mortars by using partial least squares regression multivariate calibration models constructed from NIR spectroscopic data. The additives are used to expedite setting and increase cohesion between particles in the mortar. In order to ensure that the sample set contained natural variability in the samples, we used a methodology based on experimental design to construct a representative set of samples. This novel design is based on a hexagonal antiprism that encompasses the concentration ranges spanned by the analytes and the variability inherent in each additive. The D-optimality criterion was used to obtain various combinations between Ad1 and Ad2 additive classes. The partial least squares calibration models thus constructed for each additive provided accurate predictions: the intercept and the slope of the plots of predicted values versus reference values for each additive were close to 0 and 1, respectively, and their confidence ranges included the respective value. The ensuing analytical methods were validated by using an external sample set.
A simple, fast capillary electrophoresis method for determining the total ketoprofen content in a... more A simple, fast capillary electrophoresis method for determining the total ketoprofen content in an oral pharmaceutical formulation is proposed. The addition of 75 mM of heptakis(tri- O-methyl)-beta-cyclodextrin to the background electrolyte allows the quantitation of the enantiomeric impurity of ( R)-(-)-ketoprofen contained in the formulation. A relative limit of detection is proposed as a measure of the lowest detectable enantiomeric impurity and the results show that the method can detect the minor enantiomer at levels as low as 0.04% in ( S)-(+)-ketoprofen. The chiral method was validated following ICH recommendations and the quality parameters obtained show the suitability of the proposed method. The analysis of samples examined during the course of a stability study under chiral and achiral conditions revealed that the total ketoprofen content did not change significantly with time and the enantiomeric impurity range was 0.1-0.4%.
Journal of chromatography. B, Biomedical sciences and applications, Jan 5, 2001
Pharmaceutical preparations usually contain preservatives and sweeteners. When parabens are used ... more Pharmaceutical preparations usually contain preservatives and sweeteners. When parabens are used as preservatives and a polyol as a sweetener, a transesterification reaction may happen, yielding the transester polyol-paraben. The products formed in the transesterification reaction of methylparaben and sorbitol were analyzed by micellar electrokinetic chromatography and by HPLC. Up to six positional isomers of sorbitolparaben (SPB) can be produced. However, only three peaks were found by HPLC. The higher efficiency and resolution power of MEKC allowed one to resolve five peaks. Results were compared with those obtained by capillary zone electrophoresis in borate buffer, where the separation of isomers occurred in a different way, because of a complexation between SPB and borate.
The growing interest of the pharmaceutical industry in Near Infrared-Chemical Imaging (NIR-CI) is... more The growing interest of the pharmaceutical industry in Near Infrared-Chemical Imaging (NIR-CI) is a result of its high usefulness for quality control analyses of drugs throughout their production process (particularly of its non-destructive nature and expeditious data acquisition). In this work, the concentration and distribution of the major and minor components of pharmaceutical tablets are determined and the spatial distribution from the internal and external sides has been obtained. In addition, the same NIR-CI allowed the coating thickness and its surface distribution to be quantified. Images were processed to extract the target data and calibration models constructed using the Partial Least Squares (PLS) algorithms. The concentrations of Active Pharmaceutical Ingredient (API) and excipients obtained for uncoated cores were essentially identical to the nominal values of the pharmaceutical formulation. But the predictive ability of the calibration models applied to the coated tablets decreased as the coating thickness increased.
ABSTRACT Near-infrared (NIR) is a spectroscopic method based on the absorption of light in the wa... more ABSTRACT Near-infrared (NIR) is a spectroscopic method based on the absorption of light in the wavelength region between 700 and 2500 nm due to vibrations of molecular functional groups in the sample. These spectral features arise from overtones and combinations of the fundamental molecular vibrations of these groups that occur in the infrared (IR) at longer wavelengths. NIR is rich with features arising predominantly from vibrations of C–H, O–H, and N–H.(1) NIR spectra are acquired by determining the absorbance, A, of light over a continuous range of wavelengths in spectrophotometers or at several specific wavelengths in fixed-filter photometers. Absorbance is defined by the following equation: (1) where I is the signal intensity from the sample relative to the signal intensity from a reference, I0. The reference can be an empty transmission sample cell for liquids, or it can be a broadband spectral reflector, such as a white ceramic, for reflectance measurements of solids. Absorbance is usually linearly related to concentration, following Beer&#39;s Law (Equation 2): (2) where epsiv represents the molar extinction coefficient, C is the concentration of the species, and l is the optical pathlength of light through the sample. For a particular species and fixed experimental setup, epsiv and l are constants. Letting a constant, k = (epsivl)–1, then (Equation 3) (3) A principal advantage of NIR over mid-IR for process applications is the ability to use fiber optics to transmit light between the instrument and the sample over considerable distance with NIR. This permits the instrument, a potential source of ignition, to be placed in safe areas where flammable vapors exist. Only the fiber-optic probe in contact with the sample and the optical fibers that connect to the instrument need be placed in the hazardous location. A disadvantage of NIR is the characteristics of the spectra, which are typically composed of broad, overlapping peaks in comparison to IR spectra. This often requires the use of sophisticated data analysis methods that place additional demands on vendors to provide stable NIR instruments and upon manufacturers and end-users to have highly trained staff, often at the PhD level, for calibration model development, implementation, and maintenance.
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Papers by Marcelo Blanco