Innovations in Raman spectroscopic techniques provide a potential solution to current problems in pharmaceutical drug monitoring. This review aims to summarize the recent advances in the field. The developments of novel plasmonic nanoparticles continuously push the limits of Raman spectroscopic detection. In surface‐enhanced Raman spectroscopy (SERS), these particles are used for the strong local enhancement of Raman signals from pharmaceutical drugs. SERS is increasingly applied for forensic trace detection and for therapeutic drug monitoring. In combination with spatially offset Raman spectroscopy, further application fields could be addressed, e.g. in situ pharmaceutical quality testing through the packaging. Raman optical activity, which enables the thorough analysis of specific chiral properties of drugs, can also be combined with SERS for signal enhancement. Besides SERS, micro‐ and nano‐structured optical hollow fibers enable a versatile approach for Raman signal enhancement of pharmaceuticals. Within the fiber, the volume of interaction between drug molecules and laser light is increased compared with conventional methods. Advances in fiber‐enhanced Raman spectroscopy point at the high potential for continuous online drug monitoring in clinical therapeutic diagnosis. Furthermore, fiber‐array based non‐invasive Raman spectroscopic chemical imaging of tablets might find application in the detection of substandard and counterfeit drugs. The discussed techniques are promising and might soon find widespread application for the detection and monitoring of drugs in various fields.

Fiber enhanced resonance Raman spectroscopy (FERS) is introduced for chemically selective and ultrasensitive analysis of the biomolecules hematin, hemoglobin, biliverdin, and bilirubin, as well as intact red blood cells.

This work reports the development and application of two liquid-core microstructured polymer optical fibers (LC-mPOF) with different microstructure sizes. They are used in a Fiber Enhanced Raman Spectroscopy (FERS) sensing platform, with the aim of detecting glucose in aqueous solutions in the clinically relevant range for sodium-glucose co-transporter 2 (SGLT2) inhibitor therapy. The sensing platform is tested for low concentration glucose solutions using each LC mPOF. Results confirm that a significant enhancement of the Raman signal is achieved in comparison to conventional Raman spectroscopy. Additional measurements are carried out to obtain the valid measurement range, the resolution, and the limit of detection, showing that the LC-mPOF with 66-μm-diameter central hollow core has the highest potential for future clinical applications. Finally, preliminary tests successfully demonstrate glucose identification in urine.

The particle shape, size and distribution of active pharmaceutical ingredients (API) are relevant quality indicators of pharmaceutical tablets due to their high impact on the manufacturing process. Furthermore, the bioavailability of the APIs from the dosage form depends largely on these characteristics. Routinely, particle size and shape are only analyzed in the powder form, without regard to the effect of the formulation procedure on the particle characteristics. The monitoring of these parameters improves the understanding of the process; therefore, higher quality and better control over the biopharmaceutical profile can be ensured. A new fiber-array-based Raman hyperspectral imaging technique is presented for direct simultaneous in-situ monitoring of three different active pharmaceutical ingredients- acetylsalicylic acid, acetaminophen and caffeine- in analgesic tablets. This novel method enables a chemically selective, noninvasive assessment of the distribution of the active ingredients down to 1 µm spatial resolution. The occurrence of spherical and needle-like particles, as well as agglomerations and the respective particle size ranges, were rapidly determined for two commercially available analgesic tablet types. Subtle differences were observed in comparison between these two tablets. Higher amounts of acetaminophen were visible, more needle-shaped and bigger acetylsalicylic acid particles, and a higher incidence of bigger agglomerations were found in one of the analgesic tablets.

Sepsis and septic shock exhibit a rapid course and a high fatality rate. Antibiotic treatment is time-critical and precise knowledge of the antibiotic concentration during the patients’ treatment would allow individual dose adaption. Over- and underdosing will increase the antimicrobial efficacy and reduce toxicity. We demonstrated that fiber enhanced Raman spectroscopy (FERS) can be used to detect very low concentrations of ciprofloxacin in clinically relevant doses, down to 1.5 µM. Fiber enhancement was achieved in bandgap shifted photonic crystal fibers. The high linearity between the Raman signals and the drug concentrations allows a robust calibration for drug quantification. The needed sample volume was very low (0.58 µL) and an acquisition time of 30 s allowed the rapid monitoring of ciprofloxacin levels in a less invasive way than conventional techniques. These results demonstrate that FERS has a high potential for clinical in-situ monitoring of ciprofloxacin levels.