TY - JOUR
T1 - Confocal Raman spectroscopy
T2 - Evaluation of a non-invasive technique for the detection of topically applied ketorolac tromethamine in vitro and in vivo
AU - Bertens, Christian J. F.
AU - Zhang, Shuo
AU - Erckens, Roel J.
AU - van den Biggelaar, Frank J. H. M.
AU - Berendschot, Tos T. J. M.
AU - Webers, Carroll A. B.
AU - Nuijts, Rudy M. M. A.
AU - Gijs, Marlies
PY - 2019/10/30
Y1 - 2019/10/30
N2 - Current information about the pharmacokinetics of an ocular drug can only be achieved by invasive sampling. However, confocal Raman spectroscopy bears the potential to quantify drug concentrations non-invasively. In this project, we evaluated the detection and quantification of ocular ketorolac tromethamine levels with confocal Raman spectroscopy after topical administration.Confocal Raman spectroscopy and high-performance liquid chromatography (HPLC) were compared in terms of sensitivity of detection. Enucleated pig eyes were treated with different concentrations of ketorolac. Hereafter, ketorolac concentrations in the aqueous humor of pig eyes were analyzed by confocal Raman spectroscopy and HPLC.Subsequently, twelve rabbits were treated with Acular (TM) for four weeks. At several time points, ketorolac concentrations in aqueous humor of the rabbits were measured by confocal Raman spectroscopy followed by drawing an aqueous humor sample for HPLC analysis.In ketorolac treated pig eyes, both ex vivo Raman spectroscopy as well as HPLC were able to detect ketorolac in a broad concentration range. However, in vivo confocal Raman spectroscopy in rabbits was unable to detect ketorolac in contrast to HPLC.To conclude, confocal Raman spectroscopy has the capacity to detect ketorolac tromethamine in vitro, but currently lacks sensitivity for in vivo detection.
AB - Current information about the pharmacokinetics of an ocular drug can only be achieved by invasive sampling. However, confocal Raman spectroscopy bears the potential to quantify drug concentrations non-invasively. In this project, we evaluated the detection and quantification of ocular ketorolac tromethamine levels with confocal Raman spectroscopy after topical administration.Confocal Raman spectroscopy and high-performance liquid chromatography (HPLC) were compared in terms of sensitivity of detection. Enucleated pig eyes were treated with different concentrations of ketorolac. Hereafter, ketorolac concentrations in the aqueous humor of pig eyes were analyzed by confocal Raman spectroscopy and HPLC.Subsequently, twelve rabbits were treated with Acular (TM) for four weeks. At several time points, ketorolac concentrations in aqueous humor of the rabbits were measured by confocal Raman spectroscopy followed by drawing an aqueous humor sample for HPLC analysis.In ketorolac treated pig eyes, both ex vivo Raman spectroscopy as well as HPLC were able to detect ketorolac in a broad concentration range. However, in vivo confocal Raman spectroscopy in rabbits was unable to detect ketorolac in contrast to HPLC.To conclude, confocal Raman spectroscopy has the capacity to detect ketorolac tromethamine in vitro, but currently lacks sensitivity for in vivo detection.
KW - Raman spectroscopy
KW - High-performance liquid chromatography
KW - In vivo drug detection
KW - Ketorolac tromethamine
KW - Non-invasive drug detection
KW - DRUG-DELIVERY
KW - OCULAR TISSUE
KW - SPECTRA
KW - CONTAMINANTS
KW - ABSORPTION
KW - ALGORITHM
U2 - 10.1016/j.ijpharm.2019.118641
DO - 10.1016/j.ijpharm.2019.118641
M3 - Article
C2 - 31446026
SN - 0378-5173
VL - 570
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 118641
ER -