Development of Rapid Analytical Methods in the Laboratory of Pharmaceutical Analytical Chemistry (LCAP)

Abstract

The use of rapid and ultra-rapid analytical methods in the pharmaceutical domain is mandatory in the drug discovery, drug development, and quality control steps. Liquid chromatography (LC) and capillary electrophoresis (CE) are therefore particularly studied in the Laboratory of Pharmaceutical Analytical Chemistry (LCAP) to perform fast and ultra-fast analyses of drugs present in different matrices. Due to its sensitivity and selectivity, mass spectrometry (MS) is considered today as the gold standard in pharmaceutical analysis and has been generally used as the detector of choice for performing rapid analyses. This article gives a survey of the applied strategies achieved in the LCAP for the last five years such as: use of new chromatographic supports and small columns in LC; development of column switching techniques with extraction supports compatible with the direct injection of biological matrices; use of immobilized enzyme reactors for rapid protein digestion; enhancement of electrophoretic mobility and development of different injection procedures in CE.Keywords: Capillary electrophoresis · Fast analysis · Liquid chromatography · Mass spectrometry · Sample preparation · Ultra-fast analysis number of samples. Furthermore, the delay to provide analytical responses should be as short as possible. Therefore, new rapid and efficient procedures have to be used for qualitative and quantitative analysis.The analytical techniques mainly used to screen and perform quantitative determination are immunoassay, spectroscopy, and separation tools such as chromatography and electrophoresis. The Laboratory of Pharmaceutical Analytical Chemistry (LCAP) is mainly involved in the development of liquid chromatography (LC) and electrophoretic techniques such as capillary electrophoresis (CE) for the analysis of drugs and metabolites in pharmaceutical formulations as well as in biological matrices. With both techniques coupled with different methods of detection, it is possible to perform very rapid, efficient, and sensitive analyses. Rapid Liquid ChromatographyLC is often considered as the method of choice for quantitative determination of drugs and related substances. However, conventional analysis times are usually longer than 10 min. As reported in the literature, rapid or fast methods are relative terms depending on the analyst and the requirement. Ultra-fast or ultra-rapid methods can be defined by cycle times less than 1 min (including column reconditioning), and fast or rapid methods by cycle times less than 5 min. In order to carry out rapid analyses, different strategies can be applied as presented in Fig. 1.The use of short columns (3-5 cm) to decrease the analyte retention volume and the increase of the flow rate are the simplest approaches to reduce the analysis time. However, both can compromise the chromatographic performance. Because the column reduction could lead to an important loss in efficiency, particle size should be simultaneously decreased or other chromatographic material could be used.Thus, ...

Developments in Fast Liquid Chromatographic Analysis of Pharmaceuticals

“…[2] In practice, in Fast LC method development, all factors are not changed simultaneously, but rather in a step-by-step fashion to optimize the separation with the goal to reduce the analysis time to as short as possible without losing resolution of the peaks of interest. [3] The theoretical efficiency of a column is proportional to the column length and inversely proportional to particle size. Therefore, the column length to particle size ratio should be kept approximately the same to achieve comparable efficiency values in the development of Fast LC methods.…”