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RETRACTED ARTICLE: Analysis of loxoprofen in tablets, patches, and equine urine as tert-butyldimethylsilyl derivative by gas chromatography-mass spectrometry

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This article was retracted on 01 February 2019

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Abstract

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.

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Change history

  • 01 February 2019

    The authors have retracted this article [1] because after publication they became aware that the equine urine samples analysed for loxoprofen in this study were in fact equine plasma samples. Therefore the results and conclusions of this article cannot be relied upon. All authors agree to this retraction.

References

  • 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 7:198–203

    Google Scholar 

  • Chen X, Zhao Q, Hitsu E, Jiang J, Zhong W, Matsuzawa T, Hu P (2014) Dermatopharmacokinetic bioequivalence study of two types of topical patches containing loxoprofen sodium. Int J Clin Pharmacol Ther 52(10):927–932. https://doi.org/10.5414/CP202165

    Article  CAS  PubMed  Google 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

    Article  CAS  Google Scholar 

  • Choo KS, Kim IW, Jung JK, Suh YG, Chung SJ, Lee MH, Shim CK (2001) Simultaneous determination of loxoprofen and its diastereomeric alcohol metabolites in human plasma and urine by a simple HPLC-UV detection method. J Pharm Biomed Anal 25:639–650 PMID: 11377045

    Article  CAS  Google Scholar 

  • Dumasia MC, Ginn A, Hyde W, Peterson J, Houghton E (2003) Detection and identification of carprofen and its in vivo metabolites in greyhound urine by capillary gas chromatography-mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 788:297–307 PMID: 12705970

    Article  CAS  Google 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):19–24

    Google 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Helmy SA (2013) Pharmacokinetics and bioequivalence evaluation of 2 loxoprofen tablets in healthy egyptian male volunteers. Clin Pharmacol Drug Dev 2(2):173–177. https://doi.org/10.1002/cpdd.15

    Article  CAS  PubMed  Google 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

    Article  CAS  PubMed  Google Scholar 

  • Kim KR, Yoon HR (1996) Rapid screening for acidic non-steroidal anti-inflammatory drugs in urine by gas chromatography-mass spectrometry in the selected-ion monitoring mode. J Chromatogr B Biomed Appl 682:55–66 PMID: 8832425

    Article  CAS  Google Scholar 

  • Lee HW, Ji HY, Sohn DH, Kim SM, Lee YB, Lee HS (2009) Liquid chromatography-tandem mass spectrometry method of loxoprofen in human plasma. Biomed Chromatogr 23(7):714–718. https://doi.org/10.1002/bmc.1175

    Article  CAS  PubMed  Google Scholar 

  • Lees P, Landoni MF (2002) Pharmacodynamics and enantioselective pharmacokinetics of racemic carprofen in the horse. J Vet Pharmacol Ther 25:433–448 PMID: 12485349

    Article  CAS  Google Scholar 

  • Maurer HH (1999) Systematic toxicological analysis procedures for acidic drugs and/or metabolites relevant to clinical and forensic toxicology and/or doping control. J Chromatogr B Biomed Sci Appl 733:3–25 PMID: 10572972

    Article  CAS  Google 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

    Article  CAS  PubMed  Google Scholar 

  • Paik MJ, Nguyen DT, Kim KR (2004) Enantioseparation of flurbiprofen and ketoprofen in patches and in urine excretions by achiral gas chromatography. Arch Pharm Res 27:1295–1301 PMID: 15646806

    Article  CAS  Google Scholar 

  • Soraci AL, Tapia O, Garcia J (2005) Pharmacokinetics and synovial fluid concentrations of flurbiprofen enantiomers in horses: chiral inversion. J Vet Pharmacol Ther 28:65–70 PMID: 15720517

    Article  CAS  Google 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

    Article  CAS  Google Scholar 

  • Tsitsimpikou C, Spyridaki MH, Georgoulakis I, Kouretas D, Konstantinidou M, Georgakopoulos CG (2001) Elimination profiles of flurbiprofen and its metabolites in equine urine for doping analysis. Talanta 55:1173–1180 PMID: 18968470

    Article  CAS  Google Scholar 

  • Verde CR, Simpson MI, Frigoli A, Landoni MF (2001) Enantiospecific pharmacokinetics of ketoprofen in plasma and synovial fluid of horses with acute synovitis. J Vet Pharmacol Ther 24:179–185 PMID: 11442795

    Article  CAS  Google Scholar 

  • Yu NH, Ho EN, Tang FP, Wan TS, Wong AS (2008) Comprehensive screening of acidic and neutral drugs in equine plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr A 1189:426–434 PMID: 18054785

    Article  CAS  Google Scholar 

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Acknowledgements

This paper was supported by Sunchon National University Research Fund in 2016.

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Correspondence to Wonjae Lee or Man-Jeong Paik.

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The authors declare that they have no conflict of interest.

Additional information

The authors have retracted this article because after publication they became aware that the equine urine samples analysed for loxoprofen in this study were in fact equine plasma samples. Therefore the results and conclusions of this article cannot be relied upon. All authors agree to this retraction.

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Kim, Y., Seo, C., Oh, S. et al. RETRACTED ARTICLE: Analysis of loxoprofen in tablets, patches, and equine urine as tert-butyldimethylsilyl derivative by gas chromatography-mass spectrometry. Arch. Pharm. Res. 41, 459–466 (2018). https://doi.org/10.1007/s12272-018-1023-5

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  • DOI: https://doi.org/10.1007/s12272-018-1023-5

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