Identification of degradation products in loxoprofen sodium adhesive tapes by liquid chromatography-mass spectrometry and dynamic pressurized liquid extraction-solid-phase extraction coupled to liquid chromatography-nuclear magnetic resonance spectroscopy.
Rapid and unambiguous identification of three degradation products (DP-1, DP-2 and DP-3) found in heat-stressed loxoprofen sodium adhesive tapes (Loxonin tapes) was achieved by LC-MS and dynamic pressurized liquid extraction (PLE)-solid-phase extraction (SPE) coupled to LC-NMR without complicated isolation or purification processes. The molecular formulae of the degradation products were determined by accurate mass measurements and product ion analyses and on-line hydrogen/deuterium (H/D) exchange experiments provided information about changes in the degradation of loxoprofen. To compensate for the low sensitivity of NMR, on-line dynamic PLE-SPE was employed and higher concentrations of degradation products trapped on the SPE column were afforded in a shorter time than they would be in such time-consuming sample preparations as pre-concentration after extraction. The loop-storage procedure was used in the LC-NMR analysis to allow the acquisition of the (1)H spectra of the three degradation products in one chromatographic run without affecting the peak separation and to avoid the carry-over of previously eluted DP-1 of high concentration by washing the NMR detection cell prior to the measurement of the DP-2 spectrum. Based on the resulting (1)H NMR spectra in combination with the MS results, DP-1 was successfully identified as an oxidation product having an oxodicarboxylic acid structure formed by the cleavage of the cyclopentanone ring of loxoprofen, DP-2 as a cyclopentanone ring-hydroxylated loxoprofen and DP-3 as a loxoprofen l-menthol ester.
Murakami
Tomonori
T
Analytical and Quality Evaluation Research Laboratories, Daiichi-Sankyo Co., Ltd., 1-12-1 Shinomiya, Hiratsuka, Kanagawa 254-0014, Japan. murakami.tomonori.a5@daiichisankyo.co.jp
Kawasaki
Takao
T
Takemura
Akira
A
Fukutsu
Naoto
N
Kishi
Naoyuki
N
Kusu
Fumiyo
F
D000269:Adhesives; D002853:Chromatography, Liquid / Q000379:methods*; D006358:Hot Temperature; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D010666:Phenylpropionates / Q000032:analysis* / Q000737:chemistry; D052616:Solid Phase Extraction / Q000379:methods*
D000269:Adhesives; D010666:Phenylpropionates; C040656:loxoprofen