Identification of degradation products in loxoprofen sodium adhesive tapes by liquid chromatography–mass spectrometry and dynamic pressurized liquid extraction–solid-phase extraction cou

详细信息    查看全文

• 作者：Tomonori Murakami ; Takao Kawasaki ; Akira Takemura ; Naoto Fukutsu ; Naoyuki Kishi ; Fumiyo Kusu
• 关键词：LC– ; MS ; Pressurized liquid extraction ; Solid-phase extraction ; LC– ; NMR ; Identification ; Degradation product ; Loxoprofen sodium adhesive tape
• 刊名：Journal of Chromatography A
• 出版年：2008
• 出版时间：24 October 2008
• 年：2008
• 卷：1208
• 期：1-2
• 页码：164-174
• 全文大小：418 K

文摘

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 ¹H 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 ¹H 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.