RETRACTED ARTICLE: Analysis of loxoprofen in tablets, patches, and equine urine as tert-butyldimethylsilyl derivative by gas chromatography-mass spectrometry
Loxoprofen is a non-steroidal anti-inflammatory drug of the 2-arylpropionic acid type, which has used to treat musculoskeletal disorders in the horse racing industry. However, it has also used illicitly to mask clinical signs of inflammation and pain in racehorses. Thus, its accurate analysis has become an important issue in horse doping laboratories. In this study, an analytical method of loxoprofen was developed as tert-butyldimethylsilyl (TBDMS) derivative by gas chromatography-mass spectrometry (GC–MS). Characteristic fragment ions of [M-15], [M-57], and [M-139] permitted the accurate and selective detection of loxoprofen. Under optimal conditions, this method showed good linearity (r ≥ 0.999) in the range of 10–500 ng/mL, repeatability (% relative standard deviation = 5.6–8.5), and accuracy (% relative error = − 0.3–0.9) with a detection limit of 1.0 ng. When applied to the analysis of loxoprofen in tablet and patch products, loxoprofen was positively identified as TBDMS derivative by GC–MS. The present method provided rapid and accurate determination of loxoprofen in patch and tablet products. Levels of loxoprofen were highest in equine urine at 0.5 and 1 h after oral administration with single dose (3 mg/kg) to three horses, and then rapidly reduced to below the lower limit of quantification at 24 h. Therefore, the present method will be useful for the pharmacokinetic study and doping tests for loxoprofen and other similar acidic drugs in horses.
KeywordsLoxoprofen tert-Butyldimethylsilyl derivative Gas chromatography-mass spectrometry Tablet Patch Equine urine
This paper was supported by Sunchon National University Research Fund in 2016.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Chae J, Jeon H, Lee S, Jeong N, Kim S, Kim N, Cho K, Kim D (1999) Anti-inflammatory and analgesic activites, and plasma concentration of loxoprofen sodium plasters. J Appl Phamacol 7:198–203Google Scholar
- Cho HY, Park CH, Lee YB (2006) Direct and simultaneous analysis of loxoprofen and its diastereometric alcohol metabolites in human serum by on-line column switching liquid chromatography and its application to a pharmacokinetic study. J Chromatogr B Anal Technol Biomed Life Sci 835:27–34 PMID: 16563885 CrossRefGoogle Scholar
- Ha SW, Kim S, Yoon JY, Park YT, Seo JK, Park ES, Yuk SH, Shin BC, Cho SH (2012) Preparation and evaluation of transdermal patch containing loxopropen sodium. Biomater Res 16(1):19–24Google Scholar
- Hamaguchi M, Seno T, Yamamoto A, Kohno M, Kadoya M, Ishino H, Ashihara E, Kimura S, Tsubakimoto Y, Takata H (2010) Loxoprofen sodium, a non-selective NSAID, reduces atherosclerosis in mice by reducing inflammation. J Clin Biochem Nutr 47:138–147. https://doi.org/10.3164/jcbn.10-33 CrossRefPubMedPubMedCentralGoogle Scholar
- Hirosawa M, Sambe T, Uchida N, Lee XP, Sato K, Kobayashi S (2015) Determination of nonsteroidal anti-inflammatory drugs in human tear and plasma samples using ultra-fast liquid chromatography-tandem mass spectrometry. Jpn J Ophthalmol 59(5):364–371. https://doi.org/10.1007/s10384-015-0389-x CrossRefPubMedGoogle Scholar
- Nemoto T, Lee XP, Kumazawa T, Hasegawa C, Fujishiro M, Marumo A, Shouji Y, Inagaki K, Sato K (2014) High-throughput determination of nonsteroidal anti-inflammatory drugs in human plasma by HILIC-MS/MS. J Pharm Biomed Anal 88:71–80. https://doi.org/10.1016/j.jpba.2013.08.023 CrossRefPubMedGoogle Scholar
- Takeda A, Tanaka H, Shinohara T, Ohtake I (2001) Systematic analysis of acid, neutral and basic drugs in horse plasma by combination of solid-phase extraction, non-aqueous partitioning and gas chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl 758:235–248 PMID: 11486834 CrossRefGoogle Scholar