The use of Raman spectroscopy in a hospital pharmacy setting

The goal of this research is to demonstrate how Raman microscopy and spectroscopy can be used for quality control and improved patient safety in a hospital pharmacy setting.

Methods
The hospital pharmacy associated with the national hospital in Norway, recently acquired a fully automated WITec Alpha300R Apyron Confocal Raman Microscope. After Installation Qualification (IQ) and Operational Qualification (OP) by the supplier, Performance Qualification (PQ) was carried out according to Ph. Eur. 2.2.48. Raman Spectroscopy. The wavenumber scale was verified using paracetamol for equipment qualification CRS and the spectral resolution was verified using calcium carbonate for equipment qualification CRS. Next, an in-house database consisting of active pharmaceutical ingredients (API) and excipients used in our production, as well as the most commonly used APIs in the clinic, was created. The instrument and in-house database were further used to develop methods to identify raw materials upon receipt, large area scans of pharmacy-made products, as well as identification of precipitated API in patient tubes.

Results
Methods for identification of incoming phenobarbital and sodium phenobarbital were successfully developed and validated with respect to robustness, specificity and system suitability. Large area scan of suspension suppositories identified areas consisting solely of the API acetylsalicylic acid and solely of hard fat, as well as areas where the two ingredients were mixed at different ratios. When the tube consisting of a precipitate was brought down from the clinic and put directly on the Raman instrument, a Raman spectrum with a hit quality index of > 80 towards midazolam, was recorded.

Discussion
Raman microscopy and spectroscopy is a fast method, requiring minimal sample preparation. Raman spectroscopy is especially powerful on dry samples, when used for identification purposes. The ability to separate phenobarbital from sodium phenobarbital and other related substances, illustrates the high discriminatory capabilities of the technique. When large area scans of various surfaces were carried out, mapping at a molecular level was achieved. In addition, the laser is able to penetrate plastics and other transparent materials, identifying precipitated APIs when still inside the infusion tube.

Conclusion
Raman microscopy and spectroscopy have multiple areas of use in a hospital pharmacy setting. Here, we gave a few examples of how the technique`s high identification abilities, requiring minimal sample preparation and time, can be utilized.

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