RESUMEN
When Raman spectroscopy is employed for a direct in situ determination of ingredient concentration for a product stored in a glass container, minimization of the interfering glass background in the collected spectrum is demanding to secure a more accurate analysis. To meet this request, an axially slanted illumination (ASI) scheme slantingly irradiating laser on the headspace side of a glass container and positioning a detector beneath the container was demonstrated in this study. This ASI scheme was basically designed to increase the distance between the laser illumination spot and detector location to minimize the number of glass photons reaching the detector. The analytical utility of the scheme was evaluated for the determination of gemcitabine concentration (42.9-58.2 wt%) in the gemcitabine injection powder housed in a glass container. Using the ASI scheme, the spectral features of the gemcitabine powder became distinct with only a weak underlying glass background signal. For comparative purpose, when an axially perpendicular offset (APO) scheme perpendicularly irradiating laser on the side wall where the sample was filled was used, the magnitude of glass background was higher, and the most intense gemcitabine peak was largely buried in the glass peak. The accuracy for determination of gemcitabine concentration using the ASI scheme was superior with an error of 0.20 wt%, while 0.33 wt% with employing the APO scheme. Overall, this study demonstrates that the ASI scheme is a potentially versatile Raman spectroscopic tool for fast non-sampling analysis of other products stored in a glass container.
Asunto(s)
Iluminación , Espectrometría Raman , Desoxicitidina/análogos & derivados , Vidrio , Rayos Láser , Polvos , GemcitabinaRESUMEN
This study was conducted to develop an in-line near-infrared (NIR) spectroscopy approach that allows real time quantitative analysis of the coating weight gain on a moving tablet surface during a coating process where talc is used. A holder directly inserting a diffuse reflectance probe into a coating pan was designed, and the optimal measurement conditions were identified using the design of experiments (DoE). The surface of the probe was kept clean of coating droplets at a maximum distance between the probe and the holder of 272.5 mm, leading to the acquisition of accurate spectral data. Under this condition, partial least squares regression (PLSR) was developed using the spectra from 7197 to 6233 cm-1, which covers the specific peaks for the core tablet and the coating solution. Under the same conditions, least squares regression (LSR) was developed using the univariate predictive analysis of the single absorption spectrum of talc at 7181 cm-1. In a comparison of the accuracy of the two models, PLSR was found to be more accurate as a result of testing the significance of differences between these distributions in terms of the root mean square errors of prediction (RMSEP) using a randomization t-test. Additionally, it confirmed that the predicted weight gain using NIR spectroscopy was correlated with the coating thickness measured using micro-CT. In conclusion, this study developed an in-line NIR measurement approach for the real-time monitoring of the coating weight gain of tablets and optimized the conditions by evaluating the effect of various factors.
Asunto(s)
Espectroscopía Infrarroja Corta , Aumento de Peso , Calibración , Composición de Medicamentos , Humanos , Análisis de los Mínimos Cuadrados , Distribución Aleatoria , ComprimidosRESUMEN
Protective chemical coatings are deposited on drugs during the manufacturing process for the purpose of controlling the pharmacokinetics of active pharmaceutical ingredients (APIs). Although manufacturers attempt to coat all the tablets uniformly, the film thickness of an individual drug is statistically different and depends on the measuring position of the anisotropic structure, and analytical methods for measuring coating thickness must be robust to statistical and geometrical aberrations. Herein, we demonstrate that a spatially offset Raman-spectroscopy-based line mapping method offered excellent calibration and prediction of the coating thickness of 270 acetaminophen ( N-acetyl-para-aminophenol, paracetamol) tablets. Raman-scattered light resurfaced back from the coating and APIs, and offset-resolved spectra were projected according to the vertical positions in an imaging sensor. The Raman intensity ratio between the coating substance and the inner APIs is a key parameter in the analysis, and its variation with respect to the spatial offset is proportional to the coating thickness and duration. The results of this study have implications for the rapid spectroscopic thickness measurement of industrial products coated with transparent or translucent materials.
Asunto(s)
Acetaminofén/análisis , Analgésicos no Narcóticos/análisis , Excipientes/análisis , Espectrometría Raman/métodos , Comprimidos/análisis , Acetaminofén/química , Analgésicos no Narcóticos/química , Química Farmacéutica , Excipientes/química , Propiedades de Superficie , Comprimidos/químicaRESUMEN
As a training set for multivariate quantitative analysis, lab-blended powder samples are frequently used due to the facile concentration variation of the individual components. Real pharmaceutical process samples, however, are often granular in form. The different morphologies between training and process samples result in dissimilar Raman spectral features, thereby seriously deteriorating the accuracy of the analysis. To overcome this hurdle, an effective and simple strategy to make physical presentations of both training and process samples similar, called water wetting, was demonstrated in this study. Wetting potentially dismantles process granule samples into smaller aggregates, whereas lab powder samples could be somewhat aggregated by water-bridging. Thus, water wetting would produce similar morphologies of both samples. To evaluate the strategy, samples containing esomeprazole magnesium dihydrate (EMD) as an active pharmaceutical ingredient (API) and five additional components were employed. Initially, training samples were mixed with the individual components at the intended concentration ranges. A partial least squares (PLS) model developed using the Raman spectra of the training samples was inaccurate in determining EMD concentrations in the real process samples. When both training and process samples were wetted prior to analysis, accurate concentration determination was realized due to no significant difference in Raman spectral features between samples. The similar morphologies and crystallinities of the two types of wetted samples were confirmed by analyzing the corresponding SEM images and XRD patterns. The proposed strategy is versatile and expandable for further vibrational spectroscopic analysis of various other samples with different morphologies.
Asunto(s)
Descubrimiento de Drogas , Laboratorios , Espectrometría Raman/métodos , Humectabilidad , Calibración , Análisis de los Mínimos CuadradosRESUMEN
The purpose of this study was to determine the atorvastatin (ATV) content in process pharmaceutical powder sample using Raman spectroscopy. To establish the analysis method, the influence of the type of Raman measurements (back-scattering or transmission mode), preparation of calibration sample (simple admixing or granulation), sample pre-treatment (pelletization), and spectral pretreatment on the Raman spectra was investigated. The characteristic peak of the active compound was more distinctively detected in transmission Raman mode with a laser spot size of 4mm than in the back-scattering method. Preparation of calibration samples by wet granulation, identical to the actual manufacturing process, provided unchanged spectral patterns for the in process sample, with no changes and/or shifts in the spectrum. Pelletization before Raman analysis remarkably improved spectral reproducibility by decreasing the difference in density between the samples. Probabilistic quotient normalization led to accurate and consistent quantification of the ATV content in the calibration samples (standard error of cross validation: 1.21%). Moreover, the drug content in the granules obtained from five commercial batches were reliably quantified, with no statistical difference (p=0.09) with that obtained by HPLC assay. From these findings, we suggest that transmission Raman analysis may be a fast and non-invasive method for the quantification of ATV in actual manufacturing processes.
Asunto(s)
Atorvastatina/análisis , Espectrometría Raman/métodos , Calibración , Química Farmacéutica , Cromatografía Líquida de Alta Presión , Preparaciones Farmacéuticas/análisis , Polvos , Dispersión de RadiaciónRESUMEN
In this study the authors developed a real-time Process Analytical Technology (PAT) of a coating process by applying in-line Raman spectroscopy to evaluate the coating weight gain, which is a quantitative analysis of the film coating layer. The wide area illumination (WAI) Raman probe was connected to the pan coater for real-time monitoring of changes in the weight gain of coating layers. Under the proposed in-line Raman scheme, a non-contact, non-destructive analysis was performed using WAI Raman probes with a spot size of 6â¯mm. The in-line Raman probe maintained a focal length of 250â¯mm, and a compressed air line was designed to protect the lens surface from spray droplets. The Design of Experiment (DOE) was applied to identify factors affecting the Raman spectra background of laser irradiation. The factors selected for DOE were the strength of compressed air connected to the probe, and the shielding of light by the transparent door connecting the probe to the pan coater. To develop a quantitative model, partial least squares (PLS) models as multivariate calibration were developed based on the three regions showing the specificity of TiO2 individually or in combination. For the three single peaks (636â¯cm-1, 512â¯cm-1, 398â¯cm-1), least squares method (LSM) was applied to develop three univariate quantitative analysis models. One of best multivariate quantitative model having a factor of 1 gave the lowest RMSEP of 0.128, 0.129, and 0.125, respectively for prediction batches. When LSM was applied to the single peak at 636â¯cm-1, the univariate quantitative model with an R2 of 0.9863, slope of 0.5851, and y-intercept of 0.8066 had the lowest RMSEP of 0.138, 0.144, and 0.153, respectively for prediction batches. The in-line Raman spectroscopic method for the analysis of coating weight gain was verified by considering system suitability and parameters such as specificity, range, linearity, accuracy, and precision in accordance with ICH Q2 regarding method validation. The proposed in-line Raman spectroscopy can be utilized as a PAT for product quality assurance as it offers real-time monitoring of quantitative changes in coating weight gain and process end-points during the film coating process.
Asunto(s)
Excipientes/química , Comprimidos Recubiertos/química , Calibración , Composición de Medicamentos/métodos , Análisis de los Mínimos Cuadrados , Sensibilidad y Especificidad , Espectrometría Raman/métodosRESUMEN
To investigate Raman spectral features of a coated biconvex tablet under variation of its orientation respective to laser illumination, spectra of the tablet were collected by illuminating laser on 12 different locations on the tablet with 3 different illumination angles of 45, 75 and 90°. The spectral variations were more substantial when the tablet faces with engraved letters and greater surface curvature were measured, since the sampled volume of coating relative to that of a core tablet changed significantly under these circumstances as the illumination angle varied. The preliminary examination confirmed that the acquisition of tablet-representative spectra was the requisite for reliable measurement of coating thickness. Then, to mimic real monitoring of coating process, Raman spectra were directly collected on a packing of 30 tablets with repetition of random tablet packing up to 15 times and univariate models utilizing the intensity of coating peak at 638cm-1 were developed using the cumulatively averaged spectra with an average weight of the 30 tablets as a reference. To acquire less tablet orientation-sensitive spectra, a wide area illumination (WAI) scheme providing a large sampling area (28.3mm2) on a tablet with a long focal length (â¼25cm) was employed. The averaging of the first to seventh spectra, equivalently utilizing more packing-representative spectra for quantitative analysis, made the measurement of nominal coating thickness of packed tablets accurate.
Asunto(s)
Rayos Láser , Iluminación , Espectrometría Raman , Comprimidos Recubiertos , Tecnología Farmacéutica/métodosRESUMEN
We have demonstrated a simple and effective strategy, the so-called axial illumination scheme, that is able to obtain representative Raman spectra of suspension samples with minimal influence from internal particle settling. In a partially settled suspension sample, since particle concentrations at given points throughout the sample differ, the acquisition of Raman spectra representative of the entire sample composition is critically important for accurate quantitative analysis. The proposed scheme used axially irradiated laser radiation in the same or opposite direction of settling, thus allowing laser photons to migrate through the settling-induced particle-density gradient formed in the suspension and to widely interact with particles regardless of their settled locations. Therefore, transmitted Raman signals gathered opposite to the illumination could be more representative of the overall suspension composition even with partial settling. In this study, the performance of axial illumination schemes (TB (Top-to-Bottom) and BT (Bottom-to-Top) illumination) was evaluated for the determination of the aceclofenac (a non-steroidal anti-inflammatory drug) concentration in suspensions. Although the spectral features exhibited minute variations during settling, settling did not significantly degrade the accuracy of the concentration determination, thereby indicating effective acquisition of settling-tolerant Raman spectra. In addition, the characteristics of photon migration in a partially settled suspension sample were studied using a simulation based on Monte-Carlo method.
Asunto(s)
Antiinflamatorios no Esteroideos/química , Diclofenaco/análogos & derivados , Espectrometría Raman/métodos , Diclofenaco/químicaRESUMEN
This study showed near Infrared (NIR) and Raman spectroscopy with a multivariate calibration approach were very effective to determine blend uniformity end-point. A set of 36 trimebutine samples containing magnesium stearate, stearic acid, colloidal silicon oxide, talc as excipients (0.9%â¼1.8%) was acquired from six positions during blending processing with U-type blender from 0 to 30 min. Principle component analysis (PCA) with NIR and Raman spectral data was used to confirm the end-point of blending. After 30 min, the scores of principle component (PC) 1 and principle component (PC) 2 for samples moved into one point, which clearly indicated the mixture of sample became homogenous. In addition, NIR and Raman spectroscopy has been applied to the quantitative analysis of 20 trimebutine samples containing 2â¼40% in mixture granules, which divided into a calibration set of 15 samples and a prediction set of 5 samples for NIR spectral data. The standard error of calibration (SEC) and standard error of prediction (SEP) are 0.15% and 0.13%, respectively using NIR while SEC and SEP of 0.95% and 0.91% are obtained using Raman spectroscopy. The results showed the NIR and Raman spectroscopy with a multivariate calibration such as PCA and PLS provide the possibility of real time monitoring of homogeneity and content uniformity during blending process.
Asunto(s)
Parasimpatolíticos/química , Tecnología Farmacéutica , Trimebutino/química , Inteligencia Artificial , Calibración , Química Farmacéutica , Determinación de Punto Final , Estudios de Factibilidad , Análisis de los Mínimos Cuadrados , Parasimpatolíticos/análisis , Análisis de Componente Principal , Control de Calidad , Reproducibilidad de los Resultados , República de Corea , Espectroscopía Infrarroja Corta , Espectrometría Raman , Comprimidos , Trimebutino/análisisRESUMEN
FK-3000 can inhibit proliferation of carcinomas and arrest the growth of carcinoma cells through cytotoxic (apoptosis induction) and cytostatic (cell cycle arrest) effects. A rapid and sensitive assay was developed and validated using liquid chromatography-mass spectrometry (LC-MS) for FK-3000 in rat plasma. FK-3000 was extracted with ethyl acetate from rat plasma samples, and the residue containing the FK-3000 was dried in a gentle stream of nitrogen and reconstituted with acetonitrile. The FK-3000 was quantified using high-performance liquid chromatography (HPLC; Waters Alliance 2695) with a reversed phase Gemini column (3 mm × 150 mm, 5 µm; Phenomenex, USA) and a Waters Micromass ZQ detector. FK-3000 and phenazine, an internal standard (IS), were analyzed by selected ion monitoring (SIM) at m/z transitions of 418.45 and 256, respectively. A lower limit of quantification (LLOQ) of 10 ng/mL was observed, with a linear dynamic range from 10 to 10,000 ng/mL (R>0.999). The accuracy, precision, recovery, matrix effects, and stability of the assay were deemed acceptable according to the FDA guidance for industry (bioanalytical method validation). The FK-3000 concentration was measured in plasma samples up to 6 h following FK-3000 administration at an oral dose of 20 mg/kg. The findings indicate that the assay method is suitable for routine pharmacokinetic (PK) studies of FK-3000 in rats.
Asunto(s)
Alcaloides/sangre , Alcaloides/farmacocinética , Antineoplásicos Fitogénicos/sangre , Antineoplásicos Fitogénicos/farmacocinética , Cromatografía Líquida de Alta Presión , Cromatografía de Fase Inversa , Espectrometría de Masa por Ionización de Electrospray , Acetatos/química , Acetonitrilos/química , Administración Oral , Alcaloides/administración & dosificación , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Calibración , Cromatografía Líquida de Alta Presión/normas , Cromatografía de Fase Inversa/normas , Estabilidad de Medicamentos , Límite de Detección , Modelos Lineales , Masculino , Ratas , Ratas Sprague-Dawley , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Masa por Ionización de Electrospray/normasRESUMEN
Non-destructive and rapid determination methods were developed for aceclofenac controlled release (CR) tablets. The tablet is composed of two layers, rapid release and controlled release (CR) layers. The pharmaceutical manufacturing process for CR granules is very critical for dissolution control of CR tablets. During processing, a rapid and nondestructive method to test content uniformity of aceclofenac granules is required. Chemometrics using near-infrared (NIR) and Raman spectroscopy have found significant uses in quantitative analysis of pharmaceutical products in complex matrixes. Most of the pharmaceutical products can be measured directly with little or no sample preparation using these spectroscopic methods. This study showed NIR and wide area illumination Raman spectroscopy with partial least squares (PLS) was very effective for the content uniformity of granules while high performance liquid chromatography (HPLC), a conventional method, was time-consuming and ineffective for real time control. This study showed that on-line control of content uniformity control of aceclofenac CR tablets can be achieved using NIR and Raman spectroscopy.
Asunto(s)
Preparaciones de Acción Retardada/química , Diclofenaco/análogos & derivados , Espectroscopía Infrarroja Corta/métodos , Espectrometría Raman/métodos , Diclofenaco/administración & dosificación , Diclofenaco/análisis , Control de Calidad , Espectrometría Raman/instrumentación , ComprimidosRESUMEN
Direct transmission Raman measurements for analysis of pharmaceuticals in capsules are advantageous since they can be used to determine active pharmaceutical ingredient (API) concentrations in a non-destructive manner and with much less fluorescence background interference from the capsules themselves compared to conventional back-scattering measurements. If a single calibration model such as developed from spectra simply collected in glass vials could be used to determine API concentrations of samples contained in capsules of different colors rather than constructing individual models for each capsule color, the utility of transmission measurements would be further enhanced. To evaluate the feasibility, transmission Raman spectra of binary mixtures of ambroxol and lactose were collected in a glass vial and a partial least squares (PLS) model for the determination of ambroxol concentration was developed. Then, the model was directly applied to determine ambroxol concentrations of samples contained in capsules of 4 different colors (blue, green, white and yellow). Although the prediction performance was slightly degraded when the samples were placed in blue or green capsules, due to the presence of weak fluorescence, accurate determination of ambroxol was generally achieved in all cases. The prediction accuracy was also investigated when the thickness of the capsule was varied.
Asunto(s)
Ambroxol/análisis , Lactosa/análisis , Preparaciones Farmacéuticas/análisis , Calibración , Cápsulas , Color , Análisis de los Mínimos Cuadrados , Análisis Multivariante , Espectrometría RamanRESUMEN
An assay method for the determination of oltipraz, a candidate drug for the treatment of liver fibrosis and liver cirrhosis, was developed in rat plasma using a fast-flow protein precipitation (FF-PPT) method coupled with LC-MS/MS for quantification to reduce the labor and to improve the speed of analysis. The applicability of the assay to pharmacokinetic studies was also evaluated. Oltipraz and ethyl-oltipraz, an internal standard (IS), were analyzed by multiple reaction monitoring (MRM) at m/z transitions of 227â193 and 241â174, respectively. A lower limit of quantification (LLOQ) of 20 ng/mL was observed, with a linear dynamic range from 20 to 4000 ng/mL (R>0.997). The accuracy, precision, dilution, recovery, and stability of the assay were deemed acceptable according to FDA guidelines. Oltipraz concentrations were measured successfully in plasma samples up to 12h post-dose in rats that had received an oral dose of 60 mg/kg. The findings indicate that the assay method is rapid and sensitive to oltipraz, showing applicability for pharmacokinetics (PK) studies of oltipraz in other small animals, including rats.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Pirazinas/sangre , Pirazinas/farmacocinética , Espectrometría de Masas en Tándem/métodos , Animales , Calibración , Monitoreo de Drogas/métodos , Estabilidad de Medicamentos , Ratas , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tionas , TiofenosRESUMEN
CKD-501 (i.e., lobeglitazone), a potent agonist for both PPARalpha/gamma, is a new drug that has potential clinical applications in the management of type-2 diabetes. The objective of this study was to develop a rapid and sensitive method for the determination of CKD-501 in rat plasma and to assess the applicability of the assay to pharmacokinetic studies. Rat plasma samples were processed using a fast flow protein precipitation (FF-PPT) method and then introduced onto an LC-MS/MS system for quantification. The analyte and rosiglitazone, an internal standard, were analyzed by multiple reactions monitoring (MRM) at m/z transitions of 482.0-->258.0 for CKD-501 and 358.0-->135.0 for the internal standard. The lower limit of quantification (LLOQ) was determined at 50 ng/mL, with an acceptable linearity in the range from 50 to 10,000 ng/mL (R>0.999). Validation parameters such as accuracy, precision, dilution, recovery, matrix effect and stability were found to be within the acceptance criteria of the assay validation guidelines, indicating that the assay is applicable to estimating the concentration in the range studied. The concentration of CKD-501 was readily quantifiable in plasma samples up to 24 h post-dose in rats that had received an oral dose of 1 mg/kg. These observations suggest, therefore, that the validated assay can be used in pharmacokinetic studies of CKD-501 in small animals such as the rat.
Asunto(s)
Cromatografía Liquida/métodos , Pirimidinas/análisis , Espectrometría de Masas en Tándem/métodos , Tiazolidinedionas/análisis , Administración Oral , Animales , Calibración , Química Farmacéutica/métodos , Relación Dosis-Respuesta a Droga , Estabilidad de Medicamentos , Femenino , PPAR alfa/agonistas , Pirimidinas/farmacocinética , Control de Calidad , Ratas , Ratas Sprague-Dawley , Estándares de Referencia , Reproducibilidad de los Resultados , Rosiglitazona , Tiazolidinedionas/farmacocinética , Tiazolidinedionas/farmacologíaRESUMEN
A reverse-phase high performance liquid chromatography method with electrospray ionization and detection by mass spectrometry is described for the simultaneous determination of doxifluridine and its active metabolite 5-fluorouracil in monkey serum. A liquid/liquid extraction with ethyl acetate (90%) and isopropyl alcohol (10%) was used to extract simultaneously doxifluridine and 5-FU which have considerable difference in the polarity. Optimum chromatographic separation was achieved on a Agilent Zorbax C(18) (100 mm x 2.1mm, 3.5 microm) column with a mobile phase of methanol-water (20:80, v/v). The flow rate was 0.2 mL/min with total cycle time of 5 min. The lower limit of quantification (LLOQ) was validated at 10.0 ng/mL of serum for both doxifluridine and 5-FU. Accuracy and precision of quality control (QC) samples for both compounds met FDA Guidance criteria of +/-15% with average QC accuracy of 95.5-105.0% and coefficients of variation of 1.1-9.5% in the 10-2000 ng/mL concentration range. This method demonstrated adequate sensitivity, specificity, accuracy, precision, stability to support the analysis of monkey serum samples.
Asunto(s)
Antimetabolitos Antineoplásicos/sangre , Cromatografía Líquida de Alta Presión/métodos , Floxuridina/sangre , Fluorouracilo/sangre , Espectrometría de Masas en Tándem/métodos , Administración Oral , Animales , Antimetabolitos Antineoplásicos/farmacocinética , Estabilidad de Medicamentos , Floxuridina/farmacocinética , Modelos Lineales , Macaca fascicularis , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Masa por Ionización de Electrospray/métodosRESUMEN
The active pharmaceutical ingredient (ambroxol) in an intact capsule formulation has been non-destructively quantified using Raman spectroscopy. To improve the problem of insufficient representative sampling inherent in Raman measurements, we have employed a wide area illumination (WAI) scheme that enables much improved sample coverage through a circular excitation laser spot with a 6 mm diameter. One of the anticipated sources of variation for this measurement was variation in the capsule shells. However, the WAI scheme significantly decreased the spectral variation among empty capsules compared to a measurement with a traditional small-spot excitation. Therefore, measurement variations emanating from the capsule shell did not significantly influence the accuracy of the determination of ambroxol concentrations. The resulting standard error of prediction (SEP) using the WAI scheme was comparable to that from previous Raman measurements which used a conventional small-spot excitation and employed a sampling scheme that involved rotation of an ambroxol pellet. It is further noteworthy that the SEP was also similar to that obtained from the use of transmission NIR spectroscopy, which was achieved by collection of spectra of the powdered capsule contents removed from the shell. The proposed Raman measurement using the WAI scheme in this case was sufficient to achieve the quantitative measurement of the active pharmaceutical ingredient (API) content of capsules non-destructively.
Asunto(s)
Ambroxol/química , Cápsulas/química , Preparaciones Farmacéuticas/análisis , Espectrometría Raman/métodos , Ambroxol/análisis , Cápsulas/análisis , Expectorantes/análisis , Expectorantes/química , Preparaciones Farmacéuticas/químicaRESUMEN
We describe a method for determining the ambroxol content in tablets nondestructively. To obtain a reliable quantitative calibration, we prepared 20 pellet samples (ambroxol content: 8.30-16.25 wt.%) and acquired their Raman spectra while rotating the pellets. The spectra of the rotated samples reflected the compositional variations better than those that were recorded without rotation. To reduce both the baseline variations and the spectral noise simultaneously, the spectra were pre-processed using wavelet transformation (WT). Then, we used the normalization method before partial least-squares (PLS) regression to correct Raman intensity variation from laser power fluctuation. The achieved standard error of cross validation (SECV) was 0.30%. Two different datasets where Raman intensity was artificially changed were prepared and the corresponding spectra were quantitatively analyzed. The result was reproducible even if laser intensity was fairly changed. Additionally, two different commercial tablets were analyzed and the accuracy of measurement was better for a tablet that had the similar spectral features of the standard pellet samples. The proposed method can be utilized for the analysis of commercial tablets if standard tablets of various ambroxol concentrations that have the same chemical components including additives and the same physical shape of tablets are available.
Asunto(s)
Ambroxol/análisis , Espectrometría Raman/métodos , Comprimidos/análisis , Implantes de Medicamentos/análisis , Análisis de los Mínimos Cuadrados , Tecnología Farmacéutica/métodosRESUMEN
The water content of skin was determined using a FT near infrared (NIR) spectrometer. NIR diffuse reflectance spectra were collected from hairless mouse, in vitro, and from human inner arm, in vivo. It was found that the variation of NIR absorbance band 1450 nm from OH vibration of water and 1940 nm from the combination involving OH stretching and OH deformation, depending on the absolute water content of separated hairless mouse skin, in vitro, using the FT NIR spectrometer. Partial least squares regression (PLSR) was applied to develop a calibration model. The PLS model showed good correlation. For practical use of the evaluation of human skin moisture, the PLS model for human skin moisture was developed in vivo on the basis of the relative water content of stratum corneum from the conventional capacitance method. The PLS model predicted human skin moisture with a standard errors of prediction (SEP) of 3.98 at 1130-1830 nm range. These studies showed the possibility of a rapid and nondestructive skin moisture measurement using FT NIR spectrometer.
Asunto(s)
Agua Corporal/metabolismo , Piel/metabolismo , Espectroscopía Infrarroja Corta/métodos , Agua/análisis , Animales , Calibración , Humanos , Técnicas In Vitro , Ratones , Ratones Pelados , Valores de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Piel/química , Espectroscopía Infrarroja por Transformada de Fourier/métodosRESUMEN
Near-infrared (NIR) spectroscopy has been utilized to discriminate the Korean and Chinese Angelicae gigantis Radix. Decursin, one of the major ingredients in Korean Angelicae gigantis Radix, was preliminarily identified using TLC and HPLC. Decursin was then used as a unique marker component for successful discrimination between two geographical origins. Second derivative spectra were used to reduce baseline variations observed in original diffuse reflectance spectra as well as to enhance spectral features. The unique 1625 nm band of decursin in Korean samples provided clear spectral differences over Chinese samples. To develop a calibration model, soft independent modeling of class analogy (SIMCA) was used. With the use of the SIMCA model, independent sample datasets collected at two different periods were predicted. The Korean and Chinese samples were clearly identified with 100% accuracy.
Asunto(s)
Angelica/química , Raíces de Plantas/química , Espectroscopía Infrarroja Corta/métodos , China , Cromatografía Líquida de Alta Presión/métodos , Corea (Geográfico)RESUMEN
Hydrogen peroxide (H2O2) concentrations in antiseptic solutions (normally 3% H2O2) has been determined non-destructively using a portable near-infrared (NIR) analyzer. The spectral variation due to -OH band around 1400 nm in the second derivative spectra has been found as H2O2 concentration changes. Both multiple linear regression (MLR) and partial least squares (PLS) were employed to generate calibration models over the 1100-1720 nm range. The PLS calibration model showed the better calibration performance with a standard error of prediction (SEP) of 0.16%. In order to validate the developed PLS calibration model, H2O2 concentrations in commercial antiseptic solutions were predicted and compared with values from a conventional redox titration method. The results showed that NIR predictions had good correlation with conventional analysis values. The rapid and non-destructive determination of H2O2 in the antiseptic solution was successfully performed using portable NIR analyzer without any hazardous chemical solvents.