Chemical imaging of small molecules from simple to complex matrices: Quantitative approches based on Surface Enhanced Raman scattering

Conference (2013, July)

Surface Enhanced Raman scattering (SERS) allows to dramatically exalt the Raman diffusion of molecules absorbed or very closed to rough metallic surfaces while keeping their structural information. SERS ... [more ▼]

Surface Enhanced Raman scattering (SERS) allows to dramatically exalt the Raman diffusion of molecules absorbed or very closed to rough metallic surfaces while keeping their structural information. SERS chemical imaging, presenting a high specificity and sensibility, allows acquiring a visual representation of samples combining spectral and spatial measurements. This technique could become a powerful tool in pharmaceutical and biological analysis enabling to identify and quantify molecules thanks to chemometric evaluation while looking at their distribution or their interactions. In this context, SERS chemical imaging is investigated in detection or quantitative determination of molecules in pharmaceutical and biological matrices. The feasibility of making quantitative measurements using SERS is evaluated on small target molecules models such as 4-aminophenol and lactate. Firstly, a SERS method to quantify 4-aminophenol which is the primary impurity of acetaminophen coming from its degradation during the storage or from its synthesis was developed on a real pharmaceutical formulation. The standard addition method was selected as calibration method in order to take into account the matrix effect coming from the different components of the latter. Despite the well-known stability and repeatability problems of SERS, the method was thoroughly validated by means of accuracy profiles as decision tool. Moreover, this validation methodology allowed to define a first estimation of the real analytical performance of the technique. Secondly, the detection of lactate, which is a critical metabolite implicated in several metabolic disorders, was successfully tested in the physiological concentration in a simple matrix. Preliminary results for the determination of this metabolic biomarker were also very promising allowing to consider more complex matrices. Based on these results, SERS chemical imaging was implemented to detect 4-aminophenol in a pharmaceutical tablet formerly pulverised by a SERS substrate. Through this imaging technique, it was not only possible to detect the presence of the impurity at the limit of specification of 0.1% (w/w) but it was also possible to differentiate tablets comprising different concentrations of the latter. These promising results represent the first step towards quantitative measurements using SERS chemical imaging. [less ▲]

Validation methodologies of near infrared spectroscopy methods in pharmaceutical applications

in European Pharmaceutical Review (2013), 18(1), 3-6

As any analytical methods, a mandatory step at the end of the development of a near infrared spectroscopy (NIRS) method is the validation. This step enables to give enough guarantees that each future ... [more ▼]

As any analytical methods, a mandatory step at the end of the development of a near infrared spectroscopy (NIRS) method is the validation. This step enables to give enough guarantees that each future results coming from the application of the method in routine will be closed enough to the true value. However, from the literature, a minority of NIRS methods are thoroughly validated despite of the guidelines published by different group and regulatory authorities to help analyst to adequately decide if his method can be considered as valid. In this context, the aim of this review is to offer a critical overview of the different validation methodologies applied to assess the validity of quantitative methods using near infrared spectroscopy used in the field of pharmacy. [less ▲]

Development of near infrared spectroscopic methods using desirability indexes: How to select the most appropriate calibration model

Conference (2012, May 10)

In the last decade, considerable research and developments dealing with near infrared spectroscopy (NIRS) have taken place in industrial field, especially in pharmaceutical industry. This enthusiasm can ... [more ▼]

In the last decade, considerable research and developments dealing with near infrared spectroscopy (NIRS) have taken place in industrial field, especially in pharmaceutical industry. This enthusiasm can be explained by the fact that NIRS is regarded as promising and attractive tool in Process Analytical Technology (PAT) and Green Chemistry frameworks. Taking into account its non-invasive, non-destructive character, fast data acquisition and the use of probes in on-line, in-line and at-lines, this technique is expected to reach the aims of the latters. However, the development of a NIR quantitative method is not straightforward in comparison with conventional analytical techniques. Its development requires time-consuming reference methods, chemometrics and iterative heuristic approaches to build a model allowing the prediction of the analyte of interest according to the acceptance criteria consistent with the intended use of the method. Facing to the lack of objective decision rule of the traditional chemometric criteria such as R2, RMSEC, RMSECV and RMSEP, it is essential to develop innovative approaches for the selection of the most appropriate calibration model from a models plurality. In this context, a methodology using desirability indexes, such as the Fitting Model Index (FMI), based on tolerance intervals was developed in order to increase significantly the objectivity of the decision process. This latter allows to reduce dramatically the development and the validation steps and thus could ease the implementation of NIR spectroscopy in pharmaceutical industry. [less ▲]

Critical Review of Near-Infrared Spectroscopic Methods Validations in Pharmaceutical Applications

in Journal of Pharmaceutical & Biomedical Analysis (2012), 69

Based on the large number of publications reported over the past five years, near-infrared spectroscopy (NIRS) is more and more considered an attractive and promising analytical tool regarding Process ... [more ▼]

Based on the large number of publications reported over the past five years, near-infrared spectroscopy (NIRS) is more and more considered an attractive and promising analytical tool regarding Process Analytical Technology and Green Chemistry. From the reviewed literature, few of these publications present a thoroughly validated NIRS method even if some guidelines have been published by different groups and regulatory authorities. However, as any analytical method, the validation of NIRS method is a mandatory step at the end of the development in order to give enough guarantees that each of the future results during routine use will be close enough to the true value. Besides the introduction of PAT concepts in the revised document of the European Pharmacopoeia (2.2.40) dealing with near-infrared spectroscopy recently published in Pharmeuropa, it agrees very well with this mandatory step. Indeed, the latter suggests to use similar analytical performance characteristics than those required for any analytical procedure based on acceptance criteria consistent with the intended use of the method. In this context, this review gives a comprehensive and critical overview of the methodologies applied to assess the validity of quantitative NIRS methods used in pharmaceutical applications. [less ▲]