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Quantification of ketamine and norketamine in bovine plasma by liquid chromatography–tandem mass spectrometry

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Abstract
The aim of present study was to develop a rapid and reliable analytical method for quantification of ketamine and its major metabolite, norketamine, in bovine plasma. A cost-effective and high-throughput extraction procedure was combined with a sensitive and specific liquid chromatography-heated electrospray ionization-tandem mass spectrometry method. Sample preparation consisted of a protein precipitation step using methanol followed by a clean-up using a HybridSPE(A (R))-phospholipid column and further dilution by a factor 1/10 with water before injection onto the LC-MS/MS instrument. A gradient elution program was performed with 1 % formic acid in water and 0.1 % acetic acid in methanol as mobile phases. Ionization was performed by a heated electrospray ionization (h-ESI) probe operating in the positive ionization mode. Following transitions were monitored in the selected reaction monitoring mode: 238.0 > 124.9/220.0 for ketamine and 224.0 > 207.0/124.9 for norketamine. The method was validated in-house. Matrix-matched calibration graphs were prepared for ketamine and norketamine and correlation and goodness-of-fit coefficients were 0.9991 and 0.9997 and 7.7 and 4.0 %, respectively. The within- and between-run precision and accuracy were evaluated and the results fell within the ranges specified. The limit of quantification was 0.1 A mu g/mL for both analytes, whereas limits of detection were 9.6 and 3.5 ng/mL for ketamine and norketamine, respectively. The method was applied on biological samples from a pharmacokinetic study in calves and demonstrated the suitability of the method for this application.
Keywords
Norketamine, Ketamine, Calves, Plasma, LC-MS/MS, Pharmacokinetics, URINE, DEHYDRONORKETAMINE, METABOLITE, XYLAZINE, DERIVATIZATION, MIDAZOLAM

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MLA
Devreese, Mathias, et al. “Quantification of Ketamine and Norketamine in Bovine Plasma by Liquid Chromatography–Tandem Mass Spectrometry.” JOURNAL OF THE IRANIAN CHEMICAL SOCIETY, vol. 12, no. 8, 2015, pp. 1357–62, doi:10.1007/s13738-015-0601-4.
APA
Devreese, M., Rodrigo, D., Schauvliege, S., Gasthuys, F., De Backer, P., & Croubels, S. (2015). Quantification of ketamine and norketamine in bovine plasma by liquid chromatography–tandem mass spectrometry. JOURNAL OF THE IRANIAN CHEMICAL SOCIETY, 12(8), 1357–1362. https://doi.org/10.1007/s13738-015-0601-4
Chicago author-date
Devreese, Mathias, Diego Rodrigo, Stijn Schauvliege, Frank Gasthuys, Patrick De Backer, and Siska Croubels. 2015. “Quantification of Ketamine and Norketamine in Bovine Plasma by Liquid Chromatography–Tandem Mass Spectrometry.” JOURNAL OF THE IRANIAN CHEMICAL SOCIETY 12 (8): 1357–62. https://doi.org/10.1007/s13738-015-0601-4.
Chicago author-date (all authors)
Devreese, Mathias, Diego Rodrigo, Stijn Schauvliege, Frank Gasthuys, Patrick De Backer, and Siska Croubels. 2015. “Quantification of Ketamine and Norketamine in Bovine Plasma by Liquid Chromatography–Tandem Mass Spectrometry.” JOURNAL OF THE IRANIAN CHEMICAL SOCIETY 12 (8): 1357–1362. doi:10.1007/s13738-015-0601-4.
Vancouver
1.
Devreese M, Rodrigo D, Schauvliege S, Gasthuys F, De Backer P, Croubels S. Quantification of ketamine and norketamine in bovine plasma by liquid chromatography–tandem mass spectrometry. JOURNAL OF THE IRANIAN CHEMICAL SOCIETY. 2015;12(8):1357–62.
IEEE
[1]
M. Devreese, D. Rodrigo, S. Schauvliege, F. Gasthuys, P. De Backer, and S. Croubels, “Quantification of ketamine and norketamine in bovine plasma by liquid chromatography–tandem mass spectrometry,” JOURNAL OF THE IRANIAN CHEMICAL SOCIETY, vol. 12, no. 8, pp. 1357–1362, 2015.
@article{6045881,
  abstract     = {{The aim of present study was to develop a rapid and reliable analytical method for quantification of ketamine and its major metabolite, norketamine, in bovine plasma. A cost-effective and high-throughput extraction procedure was combined with a sensitive and specific liquid chromatography-heated electrospray ionization-tandem mass spectrometry method. Sample preparation consisted of a protein precipitation step using methanol followed by a clean-up using a HybridSPE(A (R))-phospholipid column and further dilution by a factor 1/10 with water before injection onto the LC-MS/MS instrument. A gradient elution program was performed with 1 % formic acid in water and 0.1 % acetic acid in methanol as mobile phases. Ionization was performed by a heated electrospray ionization (h-ESI) probe operating in the positive ionization mode. Following transitions were monitored in the selected reaction monitoring mode: 238.0 > 124.9/220.0 for ketamine and 224.0 > 207.0/124.9 for norketamine. The method was validated in-house. Matrix-matched calibration graphs were prepared for ketamine and norketamine and correlation and goodness-of-fit coefficients were 0.9991 and 0.9997 and 7.7 and 4.0 %, respectively. The within- and between-run precision and accuracy were evaluated and the results fell within the ranges specified. The limit of quantification was 0.1 A mu g/mL for both analytes, whereas limits of detection were 9.6 and 3.5 ng/mL for ketamine and norketamine, respectively. The method was applied on biological samples from a pharmacokinetic study in calves and demonstrated the suitability of the method for this application.}},
  author       = {{Devreese, Mathias and Rodrigo, Diego and Schauvliege, Stijn and Gasthuys, Frank and De Backer, Patrick and Croubels, Siska}},
  issn         = {{1735-207X}},
  journal      = {{JOURNAL OF THE IRANIAN CHEMICAL SOCIETY}},
  keywords     = {{Norketamine,Ketamine,Calves,Plasma,LC-MS/MS,Pharmacokinetics,URINE,DEHYDRONORKETAMINE,METABOLITE,XYLAZINE,DERIVATIZATION,MIDAZOLAM}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1357--1362}},
  title        = {{Quantification of ketamine and norketamine in bovine plasma by liquid chromatography–tandem mass spectrometry}},
  url          = {{http://doi.org/10.1007/s13738-015-0601-4}},
  volume       = {{12}},
  year         = {{2015}},
}

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