Development of a simple method for simultaneous determination of nine subclasses of non-steroidal anti-inflammatory drugs in milk and dairy products by ultra-performance liquid chromatography with tandem mass spectrometry

Analysis of non-steroidal anti-inflammatory drugs in milk using QuEChERS and liquid chromatography coupled to mass spectrometry: triple quadrupole versus Q-Orbitrap mass analyzers

“…These compounds may readily undergo oxidation, and the addition of ascorbic acid to prevent their oxidation has been proposed. However, this antioxidant reagent may have deleterious effects on MS/MS detection of NSAIDs [7], which can be prevented by using a relatively low concentration of ascorbic acid [9]. Adding 0.006 M ascorbic acid to the acetonitrile extraction solution markedly improved the results of PBZ and OPB, and with no relevant adverse effects on the signals of other NSAIDs.…”

“…Few confirmatory methods have been developed for analyzing NSAID in milk samples. They are normally based on liquid chromatography (LC) coupled to mass spectrometry (MS), mostly using triple quadrupole (QqQ) instruments [4][5][6][7][8][9], although the use of high resolution mass spectrometry (HRMS, i.e. time of flight MS) and gas chromatography coupled to MS have also been described [10,11].…”

“…Acetonitrile, the effect of which on protein precipitation facilitates efficient extraction, is the most widely used solvent [4][5][6]11]. However, methanol [7] as well as acetonitrile/methanol [12] or acetonitrile/ethyl acetate mixtures [9] are also employed, and good overall recovery values have been reported for all systems. A controversial issue concerning the extraction step is the addition of ascorbic acid to prevent oxidation of pyrazolones (e.g., phenylbutazone and oxyphenbutazone [11,12].…”

“…Some authors report that it does not improve recovery [5] and may even have a detrimental effect on MS detection of other analytes [7]. The use of ascorbic acid at low concentration levels could solve this drawback [9]. Since LC-MS is susceptible to matrix effects, and milk is quite a complex matrix, most methods include some clean-up of the extracts.…”

“…Since LC-MS is susceptible to matrix effects, and milk is quite a complex matrix, most methods include some clean-up of the extracts. Several strategies have been described, such as a liquid-liquid extraction with hexane to eliminate fat content [4,9], but most of the methods apply solid phase extraction (SPE) with different sorbents, depending on the set of compounds included in the method, such as amino [6], octadecyl [12], or polymeric phases [5]. In general, the clean-up step is the bottleneck of the procedure.…”