Lija Tekenbergs-Hjelte

Quantitative FT-Raman analysis of two crystal forms of a pharmaceutical compound

A pharmaceutical active compound H appears in two polymorphs, A and B, that are stable below and above room temperature, respectively. The A- and B-forms were found to have distinct FT-Raman spectra, in particular for a band at 1716 cm-1 (A-form) or 1724 cm-1 (B-form). Mixtures of A- in B-form were prepared, and the relative intensity of the characteristic bands at 1716 and 1724 cm-1 was found to be proportional to the relative amounts of A- and B-form in the mixtures. A calibration was made which was linear in the range from 1.8 to 15.4% (w/w) of A- in B-form. The results were compared with other methods for analysis of polymorphs: FT-IR spectrometry, differential scanning calorimetry, and powder X-ray diffractometry. A novel FT-Raman sample presentation method for inhomogeneous samples is presented.

Multicomponent analysis: a case report.

Three cases are described. Case 1: kinetic studies often need high time resolution measurements in order to follow the pattern of reactions taking place during the experiment. This is often laborious to achieve with the collection of fractions for chromatographic separation. Some tool for separation is, however, necessary in order to decompose the concentrations of reactants, products and intermediate species. The spectra of the intermediates may not be known at the time when the kinetic studies are needed. With unknown spectra there are still possibilities to use spectroscopy and multivariate techniques to obtain qualitative information. Case 2: it is possible to use Partial Least Squares (PLS) in order to describe the chromatographic profiles for the species even if the separation is insufficient for traditional peak measurement methods. This requires that mixtures are available with known concentrations of the species to be determined. Case 3: with modern diode array liquid chromatography detectors there is the possibility to capture the chromatogram and the spectra at the same time. The ability to reproduce the chromatographic profile between samples makes it possible to use the Generalized Rank Annihilation Method (GRAM) possible. Whereas PLS only treats one spectrum at a time, this method treats the full two-dimensional chromatogram as an entity. The GRAM calibration is claimed to be insensitive to interfering species which are not present in the calibration. Limitations are that GRAM requires a linear detector response and very good repeatability of the retention time. The use of GRAM for calibration with real samples is demonstrated.

SINGLE SAMPLE LINEARITY TEST FOR WAVELENGTH SCANNING DETECTORS IN LIQUID CHROMATOGRAPHY

Abstract With the present demands on good laboratory practice, it is essential to verify that the analytical instruments is in a good condition. This may be done by a system suitability test before each use of the instrument where the performance of the instrument is estimated for a given analytical method, or as instrument check routine at regular intervals. The linearity of a spectrophotometric detector compounds the condition of the lamp, the cell, the electronic circuitry, and the stray light into one figure. Thus the detector linearity test may be used as a method that covers multiple sources of possible errors. Hence quality testing of detectors can be made routinely every time an analytical method is used with the same injected standard as in the method. A method for linearity tests of scanning liquid chromatography detectors is developed. This method only requires the injection of one sample in the chromatographic system. The injected sample must result in a peak that spans the expected linear range of the detector. The peak must be free from other overlapping peaks. Then the linearity is estimated by principal components analysis of the spectra in the sample peak.