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Current Drug Metabolism


ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Research Article

Pharmacokinetic Study of Vadadustat and High-Resolution Mass Spectrometric Characterization of its Novel Metabolites in Equines for the Purpose of Doping Control

Author(s): Hideaki Ishii*, Mariko Shibuya, Kanichi Kusano, Yu Sone, Takahiro Kamiya, Ai Wakuno, Hideki Ito, Kenji Miyata, Fumio Sato, Taisuke Kuroda, Masayuki Yamada and Gary Ngai-Wa Leung

Volume 23, Issue 10, 2022

Published on: 13 September, 2022

Page: [850 - 865] Pages: 16

DOI: 10.2174/1389200223666220825093945

Price: $65


Background: Vadadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitor, is a substance which carries a lifetime ban in both horse racing and equestrian competition. A comprehensive metabolic study of vadadustat in horses has not been previously reported.

Objective: Metabolism and elimination profiles of vadadustat in equine plasma and urine were studied for the purpose of doping control.

Methods: A nasoesophageal administration of vadadustat (3 g/day for 3 days) was conducted on three thoroughbred mares. Potential metabolites were comprehensively detected by differential analysis of full-scan mass spectral data obtained from both in vitro studies with liver homogenates and post-administration samples using liquid chromatography high-resolution mass spectrometry. The identities of metabolites were further substantiated by product ion scans. Quantification methods were developed and validated for the establishment of the excretion profiles of the total vadadustat (free and conjugates) in plasma and urine.

Results: A total of 23 in vivo and 14 in vitro metabolites (12 in common) were identified after comprehensive analysis. We found that vadadustat was mainly excreted into urine as the parent drug together with some minor conjugated metabolites. The elimination profiles of total vadadustat in post-administration plasma and urine were successfully established by using quantification methods equipped with alkaline hydrolysis for cleavage of conjugates such as methylated vadadustat, vadadustat glucuronide, and vadadustat glucoside.

Conclusion: Based on our study, for effective control of the misuse or abuse of vadadustat in horses, total vadadustat could successfully be detected for up to two weeks after administration in plasma and urine.

Keywords: Vadadustat, HIF stabilizer, doping control, equine, metabolic study, LC/ESI-HRMS.

« Previous
Graphical Abstract
Markham, A. Vadadustat: First Approval. Drugs, 2020, 80(13), 1365-1371.
[] [PMID: 32852744]
Pergola, P.E.; Spinowitz, B.S.; Hartman, C.S.; Maroni, B.J.; Haase, V.H. Vadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease. Kidney Int., 2016, 90(5), 1115-1122.
[] [PMID: 27650732]
Haase, V.H.; Chertow, G.M.; Block, G.A.; Pergola, P.E.; deGoma, E.M.; Khawaja, Z.; Sharma, A.; Maroni, B.J.; McCullough, P.A. Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents. Nephrol. Dial. Transplant., 2019, 34(1), 90-99.
[] [PMID: 29672740]
Nangaku, M.; Kondo, K.; Takabe, S.; Ueta, K.; Kaneko, G.; Otsuka, M.; Kawaguchi, Y.; Komatsu, Y. Vadadustat for anemia in chronic kid-ney disease patients on peritoneal dialysis: A phase 3 open-label study in Japan. Ther. Apher. Dial., 2021, 25(5), 642-653.
[] [PMID: 33283981]
Eckardt, K.U.; Agarwal, R.; Farag, Y.M.; Jardine, A.G.; Khawaja, Z.; Koury, M.J.; Luo, W.; Matsushita, K.; McCullough, P.A.; Parfrey, P.; Ross, G.; Sarnak, M.J.; Vargo, D.; Winkelmayer, W.C.; Chertow, G.M. Global Phase 3 programme of vadadustat for treatment of anaemia of chronic kidney disease: Rationale, study design and baseline characteristics of dialysis-dependent patients in the INNO2VATE trials. Nephrol. Dial. Transplant., 2021, 36(11), 2039-2048.
[] [PMID: 33188693]
Min, J.H.; Yang, H.; Ivan, M.; Gertler, F.; Kaelin, W.G., Jr; Pavletich, N.P. Structure of an HIF-1alpha -pVHL complex: Hydroxyproline recognition in signaling. Science, 2002, 296(5574), 1886-1889.
[] [PMID: 12004076]
Muchnik, E.; Kaplan, J. HIF prolyl hydroxylase inhibitors for anemia. Expert Opin. Investig. Drugs, 2011, 20(5), 645-656.
[] [PMID: 21406036]
Yan, L.; Colandrea, V.J.; Hale, J.J. Prolyl hydroxylase domain-containing protein inhibitors as stabilizers of hypoxia-inducible factor: Small molecule-based therapeutics for anemia. Expert Opin. Ther. Pat., 2010, 20(9), 1219-1245.
[] [PMID: 20698812]
Bunn, H.F. New agents that stimulate erythropoiesis. Blood, 2007, 109(3), 868-873.
[] [PMID: 17032916]
Chan, M.C.; Atasoylu, O.; Hodson, E.; Tumber, A.; Leung, I.K.; Chowdhury, R.; Gómez-Pérez, V.; Demetriades, M.; Rydzik, A.M.; Holt-Martyn, J.; Tian, Y.M.; Bishop, T.; Claridge, T.D.; Kawamura, A.; Pugh, C.W.; Ratcliffe, P.J.; Schofield, C.J. Potent and selective triazole-based inhibitors of the hypoxia-inducible factor prolyl-hydroxylases with activity in the murine brain. PLoS One, 2015, 10(7), e0132004.
[] [PMID: 26147748]
Beuck, S.; Schänzer, W.; Thevis, M. Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesis-stimulating agents in cur-rent and preventive doping analysis. Drug Test. Anal., 2012, 4(11), 830-845.
[] [PMID: 22362605]
Joharapurkar, A.A.; Pandya, V.B.; Patel, V.J.; Desai, R.C.; Jain, M.R. Prolyl hydroxylase inhibitors: A breakthrough in the therapy of anemia associated with chronic diseases. J. Med. Chem., 2018, 61(16), 6964-6982.
[] [PMID: 29712435]
Mazzarino, M.; Perretti, I.; Stacchini, C.; Comunità, F.; de la Torre, X.; Botrè, F. UPLC-MS-based procedures to detect prolyl-hydroxylase inhibitors of HIF in urine. J. Anal. Toxicol., 2021, 45(2), 184-194.
[] [PMID: 32435795]
Hu, C.J.; Wang, L.Y.; Chodosh, L.A.; Keith, B.; Simon, M.C. Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation. Mol. Cell. Biol., 2003, 23(24), 9361-9374.
[] [PMID: 14645546]
Elvert, G.; Kappel, A.; Heidenreich, R.; Englmeier, U.; Lanz, S.; Acker, T.; Rauter, M.; Plate, K.; Sieweke, M.; Breier, G.; Flamme, I. Coopera-tive interaction of hypoxia-inducible factor-2alpha (HIF-2alpha) and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2 (Flk-1). J. Biol. Chem., 2003, 278(9), 7520-7530.
[] [PMID: 12464608]
Semenza, G.L. A compendium of proteins that interact with HIF-1α. Exp. Cell Res., 2017, 356(2), 128-135.
[] [PMID: 28336293]
Chan, M.C.; Ilott, N.E.; Schödel, J.; Sims, D.; Tumber, A.; Lippl, K.; Mole, D.R.; Pugh, C.W.; Ratcliffe, P.J.; Ponting, C.P.; Schofield, C.J. Tuning the transcriptional response to hypoxia by inhibiting Hypoxia-inducible Factor (HIF) prolyl and asparaginyl hydroxylases. J. Biol. Chem., 2016, 291(39), 20661-20673.
[] [PMID: 27502280]
International Federation of Horseracing Authorities International agreement on breeding, racing and wagering and appendixes. 2022. Available (Accessed on: March 3, 2022).
Fédération Équestre Internationale. Equine prohibited substances list. 2022. Equine Prohibited Substances List., Available from: (Accessed on: March 3, 2022).
World Anti-Doping Agency. World anti-doping code international standard prohibited list 2022. Available from: (Accessed on: March 3, 2022).
Thevis, M.; Schänzer, W. Analytical approaches for the detection of emerging therapeutics and non-approved drugs in human doping con-trols. J. Pharm. Biomed. Anal., 2014, 101, 66-83.
[] [PMID: 24906629]
Beuck, S.; Bornatsch, W.; Lagojda, A.; Schänzer, W.; Thevis, M. Development of liquid chromatography-tandem mass spectrometry-based analytical assays for the determination of HIF stabilizers in preventive doping research. Drug Test. Anal., 2011, 3(11-12), 756-770.
[] [PMID: 22213684]
Hansson, A.; Thevis, M.; Cox, H.; Miller, G.; Eichner, D.; Bondesson, U.; Hedeland, M. Investigation of the metabolites of the HIF stabilizer FG-4592 (roxadustat) in five different in vitro models and in a human doping control sample using high resolution mass spectrometry. J. Pharm. Biomed. Anal., 2017, 134, 228-236.
[] [PMID: 27918992]
Thevis, M.; Milosovich, S.; Licea-Perez, H.; Knecht, D.; Cavalier, T.; Schänzer, W. Mass spectrometric characterization of a prolyl hydrox-ylase inhibitor GSK1278863, its bishydroxylated metabolite, and its implementation into routine doping controls. Drug Test. Anal., 2016, 8(8), 858-863.
[] [PMID: 26361079]
Dib, J.; Mongongu, C.; Buisson, C.; Molina, A.; Schänzer, W.; Thuss, U.; Thevis, M. Mass spectrometric characterization of the Hypoxia-Inducible Factor (HIF) stabilizer drug candidate BAY 85-3934 (molidustat) and its glucuronidated metabolite BAY-348, and their implemen-tation into routine doping controls. Drug Test. Anal., 2017, 9(1), 61-67.
[] [PMID: 27346747]
Eichner, D.; Van Wagoner, R.M.; Brenner, M.; Chou, J.; Leigh, S.; Wright, L.R.; Flippin, L.A.; Martinelli, M.; Krug, O.; Schänzer, W.; Thevis, M. lmplementation of the prolyl hydroxylase inhibitor Roxadustat (FG-4592) and its main metabolites into routine doping controls. Drug Test. Anal., 2017, 9(11-12), 1768-1778.
[] [PMID: 28378453]
Buisson, C.; Marchand, A.; Bailloux, I.; Lahaussois, A.; Martin, L.; Molina, A. Detection by LC-MS/MS of HIF stabilizer FG-4592 used as a new doping agent: Investigation on a positive case. J. Pharm. Biomed. Anal., 2016, 121, 181-187.
[] [PMID: 26808067]
Mikhail, E.; Siccardi, E.; Bawazir, A.; Rajesh, A.; Prathyush, S.; Al Wazani, D.M.K.; Sabeek, M.; John, T. A validated method for the quanti-fication of IOX-2, a potent prolyl hydroxylase inhibitor in equine urine and plasma using liquid chromatography-high-resolution mass spec-trometry. Drug Test. Anal., 2021, 13(6), 1178-1190.
[] [PMID: 33533201]
Mathew, B.; Philip, M.; Perwad, Z.; Karatt, T.K.; Caveney, M.R.; Subhahar, M.B.; Karakka Kal, A.K. Identification of Hypoxia-Inducible Factor (HIF) stabilizer roxadustat and its possible metabolites in thoroughbred horses for doping control. Drug Test. Anal., 2021, 13(6), 1203-1215.
[] [PMID: 33569900]
Ishii, H.; Shibuya, M.; So, Y.M.; Wong, J.K.Y.; Ho, E.N.M.; Kusano, K.; Sone, Y.; Kamiya, T.; Wakuno, A.; Ito, H.; Miyata, K.; Yamada, M.; Leung, G.N. Comprehensive metabolic study of IOX4 in equine urine and plasma using liquid chromatography/electrospray ionization Q Ex-active high-resolution mass spectrometer for the purpose of doping control. Drug Test. Anal., 2022, 14(2), 233-251.
[] [PMID: 34612014]
Ishii, H.; Shibuya, M.; So, Y.M.; Wong, J.K.Y.; Ho, E.N.M.; Kusano, K.; Sone, Y.; Kamiya, T.; Wakuno, A.; Ito, H.; Miyata, K.; Yamada, M.; Leung, G.N. Long-term monitoring of IOX4 in horse hair and its longitudinal distribution with segmental analysis using liquid chromatog-raphy/electrospray ionization Q Exactive high-resolution mass spectrometry for the purpose of doping control. Drug Test. Anal., 2022, 14(7), 1244-1254.
[] [PMID: 35195358]
Philip, M.; Mathew, B.; Karatt, T.K.; Perwad, Z.; Subhahar, M.B.; Karakka Kal, A.K. Metabolic studies of hypoxia-inducible factor stabilisers IOX2, IOX3 and IOX4 (in vitro) for doping control. Drug Test. Anal., 2021, 13(4), 794-816.
[] [PMID: 33458935]
Philip, M.; Karakka Kal, A.K.; Subhahar, M.B.; Karatt, T.K.; Mathew, B.; Perwad, Z. In vitro studies of hypoxia inducible factor-prolyl hy-droxylase inhibitors daprodustat, desidustat, and vadadustat for equine doping control. Drug Test. Anal., 2022, 14(2), 317-348.
[] [PMID: 34714596]
Pharmaceuticals and Medical Devices Agency. Assessment report for VAFSEO tablet 150 mg and 300 mg (in Japanese). Available from: (Accessed on: March 3, 2022).
Ishii, H.; Shimada, M.; Yamaguchi, H.; Mano, N. A simultaneous determination method for 5-fluorouracil and its metabolites in human plasma with linear range adjusted by in-source collision-induced dissociation using hydrophilic interaction liquid chromatography-electrospray ionization-tandem mass spectrometry. Biomed. Chromatogr., 2016, 30(11), 1882-1886.
[] [PMID: 27078498]
Ishii, H.; Yamaguchi, H.; Mano, N. Shifting the linear range in electrospray ionization by in-source collision-induced dissociation. Chem. Pharm. Bull. (Tokyo), 2016, 64(4), 356-359.
[] [PMID: 27039832]
Ishii, H.; Yamaguchi, H.; Mano, N. Expanding the versatility of a quantitative determination range adjustment technique using in-source CID in LC/MS/MS. Chromatogr., 2017, 38, 59-63.
Takasaki, S.; Tanaka, M.; Kikuchi, M.; Maekawa, M.; Kawasaki, Y.; Ito, A.; Arai, Y.; Yamaguchi, H.; Mano, N. Simultaneous analysis of oral anticancer drugs for renal cell carcinoma in human plasma using liquid chromatography/electrospray ionization tandem mass spectrometry. Biomed. Chromatogr., 2018, 32(6), e4184.
[] [PMID: 29283445]
Hirasawa, T.; Kikuchi, M.; Shigeta, K.; Takasaki, S.; Sato, Y.; Sato, T.; Ogura, J.; Onodera, K.; Fukuhara, N.; Onishi, Y.; Maekawa, M.; Mano, N. High-throughput liquid chromatography/electrospray ionization-tandem mass spectrometry method using in-source collision-induced dissociation for simultaneous quantification of imatinib, dasatinib, bosutinib, nilotinib, and ibrutinib in human plasma. Biomed. Chromatogr., 2021, 35(8), e5124.
[] [PMID: 33772839]
Sato, T.; Suzuka, M.; Sato, Y.; Iwabuchi, R.; Kobayashi, D.; Ogura, J.; Takasaki, S.; Yokota, M.; Tsukamoto, T.; Hayakawa, Y.; Kikuchi, M.; Maekawa, M.; Mano, N. Development of a simultaneous analytical method for clozapine and its metabolites in human plasma using liquid chromatography/electrospray ionization tandem mass spectrometry with linear range adjusted by in-source collision-induced dissociation. Biomed. Chromatogr., 2021, 35(7), e5094.
[] [PMID: 33599311]
Maekawa, M.; Mano, N. Cutting-edge LC-MS/MS applications in clinical mass spectrometry: Focusing on analysis of drugs and metabolites. Biomed. Chromatogr., 2022, 36(5), e5347.
[] [PMID: 35073598]
Ishii, H.; Shibuya, M.; Leung, G.N.; Yamashita, S.; Yamada, M.; Kushiro, A.; Kasashima, Y.; Okada, J.; Kawasaki, K.; Kijima-Suda, I. Meta-bolic study of GW1516 in equine urine using liquid chromatography/electrospray ionization Q-Exactive high-resolution mass spectrometry for doping control. Rapid Commun. Mass Spectrom., 2021, 35(5), e9028.
[] [PMID: 33319421]
Kuuranne, T.; Vahermo, M.; Leinonen, A.; Kostianen, R. Electrospray and atmospheric pressure chemical ionization tandem mass spectro-metric behavior of eight anabolic steroid glucuronides. J. Am. Soc. Mass Spectrom., 2000, 11(8), 722-730.
[] [PMID: 10937795]
Ward, L.C.; McCue, H.V.; Carnell, A.J. Carboxyl methyltransferases: Natural functions and potential applications in industrial biotechnology. ChemCatChem, 2021, 13, 121-128.
O’Tuathaigh, C.M.; Desbonnet, L.; Lee, P.; Waddington, J.L. Catechol-O-methyl transferase as a drug target for schizophrenia. CNS Neurol. Disord. Drug Targets, 2012, 11(3), 282-291.
[] [PMID: 22483298]
Pathania, S.; Bhatia, R.; Baldi, A.; Singh, R.; Rawal, R.K. Drug metabolizing enzymes and their inhibitors’ role in cancer resistance. Biomed. Pharmacother., 2018, 105, 53-65.
[] [PMID: 29843045]
Iyamu, I.D.; Huang, R. Mechanisms and inhibitors of nicotinamide N-methyltransferase. RSC Med Chem, 2021, 12(8), 1254-1261.
[] [PMID: 34458733]
Conery, A.R.; Rocnik, J.L.; Trojer, P. Small molecule targeting of chromatin writers in cancer. Nat. Chem. Biol., 2022, 18(2), 124-133.
[] [PMID: 34952934]
Wang, L.L.; Ren, X.X.; He, Y.; Cui, G.F.; Wei, Z.W.; Jia, J.; Cao, J.; Liu, Y.; Cong, B.; Niu, Y.; Yun, K.M. Study on the pharmacokinetics of diazepam and its metabolites in blood of Chinese People. Eur. J. Drug Metab. Pharmacokinet., 2020, 45(4), 477-485.
[] [PMID: 32219697]
Wen, Z.; Tallman, M.N.; Ali, S.Y.; Smith, P.C. UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuron-idation in human liver and intestinal microsomes: Structural characterization of phenolic and alcoholic glucuronides of etoposide and estima-tion of enzyme kinetics. Drug Metab. Dispos., 2007, 35(3), 371-380.
[] [PMID: 17151191]
Ishii, H.; Leung, G.N.; Yamashita, S.; Nagata, S.I.; Kushiro, A.; Sakai, S.; Toju, K.; Okada, J.; Kawasaki, K.; Kusano, K.; Kijima-Suda, I. Comprehensive metabolic study of nicotine in equine plasma and urine using liquid chromatography/high-resolution mass spectrometry for the identification of unique biomarkers for doping control. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2022, 1190, 123100.
[] [PMID: 35032890]
Ishii, H.; Leung, G.N.; Yamashita, S.; Nagata, S.I.; Kushiro, A.; Sakai, S.; Toju, K.; Okada, J.; Kawasaki, K.; Kusano, K.; Kijima-Suda, I. Identification of potential biomarkers in urine and plasma after consumption of tobacco product in horses. Drug Test. Anal., 2022, 14(5), 902-914.
[] [PMID: 35195357]
Schebb, N.H.; Franze, B.; Maul, R.; Ranganathan, A.; Hammock, B.D. In vitro glucuronidation of the antibacterial triclocarban and its oxida-tive metabolites. Drug Metab. Dispos., 2012, 40(1), 25-31.
[] [PMID: 21953915]
Jinno, N.; Tagashira, M.; Tsurui, K.; Yamada, S. Contribution of cytochrome P450 and UDT-glucuronosyltransferase to the metabolism of drugs containing carboxylic acid groups: Risk assessment of acylglucuronides using human hepatocytes. Xenobiotica, 2014, 44(8), 677-686.
[] [PMID: 24575896]
Hammond, T.G.; Meng, X.; Jenkins, R.E.; Maggs, J.L.; Castelazo, A.S.; Regan, S.L.; Bennett, S.N.; Earnshaw, C.J.; Aithal, G.P.; Pande, I.; Kenna, J.G.; Stachulski, A.V.; Park, B.K.; Williams, D.P. Mass spectrometric characterization of circulating covalent protein adducts derived from a drug acyl glucuronide metabolite: Multiple albumin adductions in diclofenac patients. J. Pharmacol. Exp. Ther., 2014, 350(2), 387-402.
[] [PMID: 24902585]
Ebner, T.; Heinzel, G.; Prox, A.; Beschke, K.; Wachsmuth, H. Disposition and chemical stability of telmisartan 1-O-acylglucuronide. Drug Metab. Dispos., 1999, 27(10), 1143-1149.
[PMID: 10497140]
Di Meo, F.; Steel, M.; Nicolas, P.; Marquet, P.; Duroux, J.L.; Trouillas, P. Acylglucuronide in alkaline conditions: Migration vs. hydrolysis. J. Mol. Model., 2013, 19(6), 2423-2432.
[] [PMID: 23420401]
Pedersen, L.C.; Yi, M.; Pedersen, L.G.; Kaminski, A.M. From steroid and drug metabolism to glycobiology, using sulfotransferase structures to understand and tailor function. Drug Metab. Dispos., 2022, DMDMR-2021-000478.
[] [PMID: 35197313]
Momose, T.; Maruyama, J.; Iida, T.; Goto, J.; Nambara, T. Comparative abilities and optimal conditions for beta-glycosidase enzymes to hydrolyse the glucuronide, glucoside, and N-acetylglucosaminide conjugates of bile acids. Biol. Pharm. Bull., 1997, 20(8), 828-833.
[] [PMID: 9300125]
Srinivasan, K.; Nouri, P.; Kavetskaia, O. Challenges in the indirect quantitation of acyl-glucuronide metabolites of a cardiovascular drug from complex biological mixtures in the absence of reference standards. Biomed. Chromatogr., 2010, 24(7), 759-767.
[] [PMID: 20014146]
Dieterle, W.; Faigle, J.W.; Küng, W.; Theobald, W. The metabolic fate of 14C-oxaprotiline X HCl in man. III. Stereospecific disposition. Biopharm. Drug Dispos., 1984, 5(4), 377-386.
[] [PMID: 6525444]
Dębski, H.; Wiczkowski, W.; Horbowicz, M. Effect of elicitation with iron chelate and sodium metasilicate on phenolic compounds in legume sprouts. Molecules, 2021, 26(5), 1345.
[] [PMID: 33802449]
Basiliere, S.; Kerrigan, S. Temperature and pH-dependent stability of mitragyna alkaloids. J. Anal. Toxicol., 2020, 44(4), 314-324.
[] [PMID: 31897484]
Li, J.; Ni, G.; Liu, Y.; Wang, R.; Yu, D. Long-chain fatty acid acylated derivatives of isoflavone glycosides from the rhizomes of Iris domesti-ca. Phytochemistry, 2022, 193, 112977.
[] [PMID: 34715401]
Shimokawa, S.; Iwashina, T.; Murakami, N. Flower color changes in three Japanese hibiscus species: Further quantitative variation of antho-cyanin and flavonols. Nat. Prod. Commun., 2015, 10(3), 451-452.
[] [PMID: 25924527]
Takeda, A.; Nakata, M.; Kijima-Suda, I.; Tanaka, H. In: Trial for ionization enhancement in negative ion electrospray ionisation and rapid screening of acid drugs by liquid chromatography/mass spectrometry: Proceedings of the 16th International Conference of Racing Analysts and Veterinarians, Tokyo, Japan, October 21-27, 2006; Houghton, E.; Kijima-Suda, I.; Wada, R.; Wade, J.F., Eds.; R & W Communications: Newmarket, UK, 2007, pp. 239-245.
Ishii, H.; Leung, G.N.; Yamashita, S.; Yamada, M.; Kushiro, A.; Kasashima, Y.; Okada, J.; Kawasaki, K.; Kijima-Suda, I. Doping control analysis of GW1516 in equine plasma using liquid chromatography/electrospray ionization Q-Exactive high-resolution mass spectrometry. Rapid Commun. Mass Spectrom., 2020, 34(23), e8920.
[] [PMID: 32776613]
Ishii, H.; Shibuya, M.; Leung, G.N.; Nozawa, S.; Yamashita, S.; Yamada, M.; Kushiro, A.; Kasashima, Y.; Okada, J.; Kawasaki, K.; Kijima-Suda, I. Detection and longitudinal distribution of GW1516 and its metabolites in equine hair for doping control using liquid chromatog-raphy/high-resolution mass spectrometry. Rapid Commun. Mass Spectrom., 2021, 35(8), e9050.
[] [PMID: 33470485]
Al-Rifai, Z.; Mulvey, D. Principles of total intravenous anaesthesia: Basic pharmacokinetics and model descriptions. BJA Educ., 2016, 16, 92-97.

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