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Current Pharmaceutical Analysis


ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

A Sensitive HPLC-MS/MS Method for the Quantification of Selegiline in Beagle Dog Plasma: Application to a Pharmacokinetic Study

Author(s): Hongrui Liu, Fang Chen, Bing Wang, Hao Wang, Shasha Jin, Zhou Yang, Yusheng Chen, Yingjun Quan and Xiaoqiang Xiang*

Volume 17, Issue 1, 2021

Published on: 23 August, 2019

Page: [140 - 148] Pages: 9

DOI: 10.2174/1573412915666190823102223

Price: $65


Objective: To develop a reliable and sensitive high-performance liquid chromatographytandem mass spectrometry (HPLC-MS/MS) method for the quantification of selegiline in Beagle dog plasma and apply the validated method to study the pharmacokinetics and bioavailability of oral selegiline lyophilizate in Beagle dogs.

Methods: Following alkalization with 1 M sodium hydroxide solution, selegiline and the Internal Standard (IS) zolmitriptan were extracted using tert-butyl methyl ether and separated on a CAPCELL PAK C18 column under isocratic conditions. They were detected by MS/MS using electrospray ionization (ESI) in the positive mode. Quantification was performed using multiple reaction monitoring (MRM) with transitions of m/z 188.05→90.9 for selegiline and m/z 288.05→57.95 for IS.

Results: Calibration curves were constructed in the concentration range of 0.2–200 ng/mL with a lower limit of quantification (LLOQ) of 0.21 ng/mL. The matrix effect of dog plasma on the selegiline signal ranged from 98.8 to 105.6%, and the mean extraction recovery ranged from 79.0% to 81.4% at concentrations of 1.04, 20.8, and 166 ng/mL. The intra-day precision was lower than 6.86% and the inter-day precisions were lower than 4.63%.

Conclusion: The validation results demonstrated the reliability of this bioanalytical method, which was successfully applied to study the pharmacokinetics and bioavailability of 1.25 mg of orally administered selegiline lyophilizate in Beagle dogs. The pharmacokinetic results were also compared with those obtained following intragastric (i.g.) and intravenous (i.v.) administration. Buccal delivery of selegiline was found to significantly increase its bioavailability.

Keywords: Selegiline, HPLC-MS/MS, sensitivity, pharmacokinetic, bioavailability, beagle dog.

Graphical Abstract
Magyar, K. The pharmacology of selegiline. Int. Rev. Neurobiol., 2011, 100(11), 65-84.
[] [PMID: 21971003]
Miklya, I. The significance of selegiline/(-)-deprenyl after 50 years in research and therapy (1965-2015). Mol. Psychiatry, 2016, 21(11), 1499-1503.
[] [PMID: 27480491]
Reynolds, G.P.; Riederer, P.; Rausch, W.D. Dopamine metabolism in human brain: effect of monoamine oxidase inhibition in vitro by (-)deprenyl and (+) and (-) tranylcypromine. J. Neural Transm. Suppl., 1980, 16(16), 173-178.
[] [PMID: 6776236]
Tatton, W.G.; Greenwood, C.E. Rescue of dying neurons: a new action for deprenyl in MPTP parkinsonism. J. Neurosci. Res., 1991, 30(4), 666-672.
[] [PMID: 1686284]
Kivistö, K.T.; Wang, J.S.; Backman, J.T.; Nyman, L.; Taavitsainen, P.; Anttila, M.; Neuvonen, P.J. Selegiline pharmacokinetics are unaffected by the CYP3A4 inhibitor itraconazole. Eur. J. Clin. Pharmacol., 2001, 57(1), 37-42.
[] [PMID: 11372588]
Kuriki, A.; Kumazawa, T.; Lee, X.P.; Hasegawa, C.; Kawamura, M.; Suzuki, O.; Sato, K. Simultaneous determination of selegiline and desmethylselegiline in human body fluids by headspace solid-phase microextraction and gas chromatography-mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2006, 844(2), 283-291.
[] [PMID: 16893687]
Gerlach, M.; Youdim, M.B.H.; Riederer, P. Pharmacology of selegiline. Neurology, 1996, 47(6)(Suppl. 3), S137-S145.
[] [PMID: 8959982]
Poston, K.L.; Waters, C. Zydis selegiline in the management of Parkinson’s disease. Expert Opin. Pharmacother., 2007, 8(15), 2615-2624.
[] [PMID: 17931095]
Kalász, H.; Kerecsen, L.; Knoll, J.; Pucsok, J. Chromatographic studies on the binding, action and metabolism of (-)-deprenyl. J. Chromatogr. A, 1990, 499(499), 589-599.
[] [PMID: 2108980]
Clarke, A.; Brewer, F.; Johnson, E.S.; Mallard, N.; Hartig, F.; Taylor, S.; Corn, T.H. A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition. J. Neural Transm. (Vienna), 2003, 110(11), 1241-1255.
[] [PMID: 14628189]
Strano-Rossi, S.; Colamonici, C.; Botrè, F. Parallel analysis of stimulants in saliva and urine by gas chromatography/mass spectrometry: perspectives for “in competition” anti-doping analysis. Anal. Chim. Acta, 2008, 606(2), 217-222.
[] [PMID: 18082653]
Patrick, K.S.; Nguyen, B.L.; McCallister, J.D. Gas chromatographic-mass spectrometric determination of plasma selegiline using a deuterated internal standard. J. Chromatogr. A, 1992, 583(2), 254-258.
[] [PMID: 1478990]
Salonen, J.S. Determination of the amine metabolites of selegiline in biological fluids by capillary gas chromatography. J. Chromatogr. A, 1990, 527(1), 163-168.
[] [PMID: 2114418]
Anttila, M.; Sotaniemi, E.A.; Pelkonen, O.; Rautio, A. Marked effect of liver and kidney function on the pharmacokinetics of selegiline. Clin. Pharmacol. Ther., 2005, 77(1), 54-62.
[] [PMID: 15637531]
Laine, K.; Anttila, M.; Nyman, L.; Wahlberg, A.; Bertilsson, L. CYP2C19 polymorphism is not important for the in vivo metabolism of selegiline. Eur. J. Clin. Pharmacol., 2001, 57(2), 137-142.
[] [PMID: 11417445]
La Croix, R.; Pianezzola, E.; Strolin Benedetti, M. Sensitive high-performance liquid chromatographic method for the determination of the three main metabolites of selegiline (L-deprenyl) in human plasma. J. Chromatogr. B Biomed. Appl., 1994, 656(1), 251-258.
[] [PMID: 7952037]
Mascher, H.J.; Kikuta, C.; Millendorfer, A.; Schiel, H.; Ludwig, G. Pharmacokinetics and bioequivalence of the main metabolites of selegiline: desmethylselegiline, methamphetamine and amphetamine after oral administration of selegiline. Int. J. Clin. Pharmacol. Ther., 1997, 35(1), 9-13.
[PMID: 9021435]
Pöstényi, Z.; Tekes, K.; Tóth-Molnár, E.; Kalász, H. HPLC analysis of blood-brain barrier penetration of 4-fluorodeprenyl. J. Pharm. Biomed. Anal., 2015, 102(1), 529-534.
[] [PMID: 25459953]
Saka, C. An overview of analytical methods for the determination of monoamine oxidase inhibitors in pharmaceutical formulations and biological fluids. Crit. Rev. Anal. Chem., 2017, 47(1), 1-23.
[] [PMID: 27715253]
Slawson, M.H.; Taccogno, J.L.; Foltz, R.L.; Moody, D.E. Quantitative analysis of selegiline and three metabolites (N-desmethylselegiline, methamphetamine, and amphetamine) in human plasma by high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry. J. Anal. Toxicol., 2002, 26(7), 430-437.
[] [PMID: 12422997]
Nishida, K.; Itoh, S.; Inoue, N.; Kudo, K.; Ikeda, N. High-performance liquid chromatographic-mass spectrometric determination of methamphetamine and amphetamine enantiomers, desmethylselegiline and selegiline, in hair samples of long-term methamphetamine abusers or selegiline users. J. Anal. Toxicol., 2006, 30(4), 232-237.
[] [PMID: 16803660]
Katagi, M.; Tatsuno, M.; Miki, A.; Nishikawa, M.; Nakajima, K.; Tsuchihashi, H. Simultaneous determination of selegiline-N-oxide, a new indicator for selegiline administration, and other metabolites in urine by high-performance liquid chromatography-electrospray ionization mass spectrometry. J. Chromatogr. B Biomed. Sci. Appl., 2001, 759(1), 125-133.
[] [PMID: 11499616]
Azzaro, A.J.; Ziemniak, J.; Kemper, E.; Campbell, B.J.; VanDenBerg, C. Pharmacokinetics and absolute bioavailability of selegiline following treatment of healthy subjects with the selegiline transdermal system (6 mg/24 h): a comparison with oral selegiline capsules. J. Clin. Pharmacol., 2007, 47(10), 1256-1267.
[] [PMID: 17715422]
Guidance for Industry. Bioanalytical Method Validation US Departmentof Health and HumanServices, Food and Drug Administration, Center forDrug Evaluation and Research; CDER, 2001.
Sargent, M., Ed.; Guide to Achieving Reliable Quantitative LC-MS Measurements, 1st ed; , 2013.
Li, Z.; Ding, C.; Ge, Q.; Zhou, Z.; Zhi, X.; Liu, X. Simultaneous determination of lamivudine, stavudine and nevirapine in human plasma by LC-MS/MS and its application to pharmacokinetic study in clinic. Biomed. Chromatogr., 2010, 24(9), 926-934.
[PMID: 20058328]
Heinonen, E.H.; Lammintausta, R. A review of the pharmacology of selegiline. Acta Neurol. Scand. Suppl., 1991, 136, 44-59.
[] [PMID: 1686954]
Mahmood, I.; Peters, D.K.; Mason, W.D. The pharmacokinetics and absolute bioavailability of selegiline in the dog. Biopharm. Drug Dispos., 1994, 15(8), 653-664.
[] [PMID: 7888597]

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