FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Current drug metabolism2022; 23(10); 850-865; doi: 10.2174/1389200223666220825093945

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

Abstract: 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. Conclusions: 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.
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Get Full Text
Publication Date: 2022-08-27 PubMed ID: 36017833DOI: 10.2174/1389200223666220825093945Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article investigates the metabolism and elimination profiles of the banned substance Vadadustat in horses, with the goal of enhancing doping control measures in horse racing and equestrian competition. The researchers employed liquid chromatography high-resolution mass spectrometry to detect potential metabolites following administration of Vadadustat to three thoroughbred mares. The findings showed that Vadadustat is mainly excreted in urine as the parent drug, alongside minor metabolites. These results may contribute to more effective detection methods to prevent misuse of Vadadustat in horses.

Methods

  • The study was conducted on three thoroughbred mares, administering Vadadustat through a nasoesophageal method. The dosage was at 3 grams daily for three days.
  • The potential metabolites of Vadadustat were detected using liquid chromatography high-resolution mass spectrometry. This method allowed for a comprehensive analysis of the full-scan mass spectral data obtained in vitro with liver homogenates and post-administration samples.
  • The researchers developed and validated quantification methods that helped in establishing the excretion profiles of Vadadustat (both free and conjugates) in the plasma and urine of the mares.

Findings

  • The researchers identified a total of 23 in vivo and 14 in vitro metabolites, with 12 of these metabolites common to both categories.
  • Their analysis found that Vadadustat is primarily excreted into urine as the parent drug, with some minor conjugated metabolites also present.
  • The elimination profiles of total Vadadustat in the horses’ plasma and urine were successfully established using the developed quantification methods.

Conclusions & Implications

  • The researchers suggest that total Vadadustat could be detected for up to two weeks after administration in the plasma and urine of horses.
  • The study’s findings could aid in the development of more efficient doping control measures in horse racing and equestrian competitions. This is due to the improved understanding of the metabolic and elimination profiles of the banned substance Vadadustat.

Cite This Article

APA
Ishii H, Shibuya M, Kusano K, Sone Y, Kamiya T, Wakuno A, Ito H, Miyata K, Sato F, Kuroda T, Yamada M, Leung GN. (2022). Pharmacokinetic Study of Vadadustat and High-Resolution Mass Spectrometric Characterization of its Novel Metabolites in Equines for the Purpose of Doping Control. Curr Drug Metab, 23(10), 850-865. https://doi.org/10.2174/1389200223666220825093945

Publication

Current drug metabolism
ISSN: 1875-5453
NlmUniqueID: 100960533
Country: Netherlands
Language: English
Volume: 23
Issue: 10
Pages: 850-865

Researcher Affiliations

Ishii, Hideaki
  • Drug Analysis Department, Laboratory of Racing Chemistry, 1731-2 Tsuruta-machi, Utsunomiya, Tochigi, Zip 320-0851, Japan.
  • Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Zip 980-8574, Japan.
Shibuya, Mariko
  • Drug Analysis Department, Laboratory of Racing Chemistry, 1731-2 Tsuruta-machi, Utsunomiya, Tochigi, Zip 320-0851, Japan.
Kusano, Kanichi
  • Veterinarian Section, Equine Department, Japan Racing Association, 6-11-1 Roppongi, Minato-ku, Tokyo, Zip 105-0003, Japan.
Sone, Yu
  • Veterinarian Section, Equine Department, Japan Racing Association, 6-11-1 Roppongi, Minato-ku, Tokyo, Zip 105-0003, Japan.
Kamiya, Takahiro
  • Equine Veterinary Clinic, Horse Racing School, Japan Racing Association, 835-1 Ne, Shiroi, Chiba, Zip 270-1431, Japan.
Wakuno, Ai
  • Equine Veterinary Clinic, Horse Racing School, Japan Racing Association, 835-1 Ne, Shiroi, Chiba, Zip 270-1431, Japan.
Ito, Hideki
  • Equine Veterinary Clinic, Horse Racing School, Japan Racing Association, 835-1 Ne, Shiroi, Chiba, Zip 270-1431, Japan.
Miyata, Kenji
  • JRA Equestrian Park Utsunomiya Office, 321-4 Tokamicho, Utsunomiya, Tochigi, Zip 320-0856, Japan.
Sato, Fumio
  • Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, 1400-4, Shiba, Shimotsuke, Tochigi, Zip 329-0412, Japan.
Kuroda, Taisuke
  • Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, 1400-4, Shiba, Shimotsuke, Tochigi, Zip 329-0412, Japan.
Yamada, Masayuki
  • Drug Analysis Department, Laboratory of Racing Chemistry, 1731-2 Tsuruta-machi, Utsunomiya, Tochigi, Zip 320-0851, Japan.
Leung, Gary Ngai-Wa
  • Drug Analysis Department, Laboratory of Racing Chemistry, 1731-2 Tsuruta-machi, Utsunomiya, Tochigi, Zip 320-0851, Japan.

MeSH Terms

  • Horses
  • Animals
  • Female
  • Mass Spectrometry
  • Chromatography, Liquid / methods
  • Glycine / metabolism
  • Liver / metabolism

Grant Funding

  • 2022 / JRA, Japan Racing Association

References

This article includes 69 references
  1. Markham A. Vadadustat: First Approval.. Drugs 2020 Sep;80(13):1365-1371.
    doi: 10.1007/s40265-020-01383-zpubmed: 32852744google scholar: lookup
  2. Pergola PE, Spinowitz BS, Hartman CS, Maroni BJ, Haase VH. Vadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease.. Kidney Int 2016 Nov;90(5):1115-1122.
    doi: 10.1016/j.kint.2016.07.019pubmed: 27650732google scholar: lookup
  3. Haase VH, Chertow GM, Block GA, Pergola PE, deGoma EM, Khawaja Z, Sharma A, Maroni BJ, McCullough PA. Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents.. Nephrol Dial Transplant 2019 Jan 1;34(1):90-99.
    doi: 10.1093/ndt/gfy055pubmed: 29672740google scholar: lookup
  4. Nangaku M, Kondo K, Takabe S, Ueta K, Kaneko G, Otsuka M, Kawaguchi Y, Komatsu Y. Vadadustat for anemia in chronic kidney disease patients on peritoneal dialysis: A phase 3 open-label study in Japan.. Ther Apher Dial 2021 Oct;25(5):642-653.
    doi: 10.1111/1744-9987.13611pubmed: 33283981google scholar: lookup
  5. Eckardt KU, Agarwal R, Farag YM, Jardine AG, Khawaja Z, Koury MJ, Luo W, Matsushita K, McCullough PA, Parfrey P, Ross G, Sarnak MJ, Vargo D, Winkelmayer WC, Chertow GM. 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 Nov 9;36(11):2039-2048.
    doi: 10.1093/ndt/gfaa204pubmed: 33188693google scholar: lookup
  6. Min JH, Yang H, Ivan M, Gertler F, Kaelin WG Jr, Pavletich NP. Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling.. Science 2002 Jun 7;296(5574):1886-9.
    doi: 10.1126/science.1073440pubmed: 12004076google scholar: lookup
  7. Muchnik E, Kaplan J. HIF prolyl hydroxylase inhibitors for anemia.. Expert Opin Investig Drugs 2011 May;20(5):645-56.
    doi: 10.1517/13543784.2011.566861pubmed: 21406036google scholar: lookup
  8. Yan L, Colandrea VJ, Hale JJ. Prolyl hydroxylase domain-containing protein inhibitors as stabilizers of hypoxia-inducible factor: small molecule-based therapeutics for anemia.. Expert Opin Ther Pat 2010 Sep;20(9):1219-45.
    doi: 10.1517/13543776.2010.510836pubmed: 20698812google scholar: lookup
  9. Bunn HF. New agents that stimulate erythropoiesis.. Blood 2007 Feb 1;109(3):868-73.
    doi: 10.1182/blood-2006-08-019083pubmed: 17032916google scholar: lookup
  10. Chan MC, Atasoylu O, Hodson E, Tumber A, Leung IK, Chowdhury R, Gómez-Pérez V, Demetriades M, Rydzik AM, Holt-Martyn J, Tian YM, Bishop T, Claridge TD, Kawamura A, Pugh CW, Ratcliffe PJ, Schofield CJ. 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.
    doi: 10.1371/journal.pone.0132004pubmed: 26147748google scholar: lookup
  11. Beuck S, Schänzer W, Thevis M. Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesis-stimulating agents in current and preventive doping analysis.. Drug Test Anal 2012 Nov;4(11):830-45.
    doi: 10.1002/dta.390pubmed: 22362605google scholar: lookup
  12. Joharapurkar AA, Pandya VB, Patel VJ, Desai RC, Jain MR. Prolyl Hydroxylase Inhibitors: A Breakthrough in the Therapy of Anemia Associated with Chronic Diseases.. J Med Chem 2018 Aug 23;61(16):6964-6982.
    doi: 10.1021/acs.jmedchem.7b01686pubmed: 29712435google scholar: lookup
  13. 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 Feb 13;45(2):184-194.
    doi: 10.1093/jat/bkaa055pubmed: 32435795google scholar: lookup
  14. Hu CJ, Wang LY, Chodosh LA, Keith B, Simon MC. Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation.. Mol Cell Biol 2003 Dec;23(24):9361-74.
    doi: 10.1128/MCB.23.24.9361-9374.2003pubmed: 14645546google scholar: lookup
  15. Elvert G, Kappel A, Heidenreich R, Englmeier U, Lanz S, Acker T, Rauter M, Plate K, Sieweke M, Breier G, Flamme I. Cooperative 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 Feb 28;278(9):7520-30.
    doi: 10.1074/jbc.M211298200pubmed: 12464608google scholar: lookup
  16. Semenza GL. A compendium of proteins that interact with HIF-1α.. Exp Cell Res 2017 Jul 15;356(2):128-135.
    doi: 10.1016/j.yexcr.2017.03.041pubmed: 28336293google scholar: lookup
  17. Chan MC, Ilott NE, Schödel J, Sims D, Tumber A, Lippl K, Mole DR, Pugh CW, Ratcliffe PJ, Ponting CP, Schofield CJ. Tuning the Transcriptional Response to Hypoxia by Inhibiting Hypoxia-inducible Factor (HIF) Prolyl and Asparaginyl Hydroxylases.. J Biol Chem 2016 Sep 23;291(39):20661-73.
    doi: 10.1074/jbc.M116.749291pubmed: 27502280google scholar: lookup
  18. International Federation of Horseracing Authorities. International agreement on breeding, racing and wagering and appendixes. 2022 (Accessed on: March 3, 2022).
  19. Fédération Équestre Internationale. Equine prohibited substances list. Equine Prohibited Substances List 2022 (Accessed on: March 3, 2022).
  20. World Anti-Doping Agency. World anti-doping code international standard prohibited list 2022. (Accessed on: March 3, 2022).
  21. Thevis M, Schänzer W. Analytical approaches for the detection of emerging therapeutics and non-approved drugs in human doping controls.. J Pharm Biomed Anal 2014 Dec;101:66-83.
    doi: 10.1016/j.jpba.2014.05.020pubmed: 24906629google scholar: lookup
  22. 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 Nov-Dec;3(11-12):756-70.
    doi: 10.1002/dta.365pubmed: 22213684google scholar: lookup
  23. 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 Feb 5;134:228-236.
    doi: 10.1016/j.jpba.2016.11.041pubmed: 27918992google scholar: lookup
  24. Thevis M, Milosovich S, Licea-Perez H, Knecht D, Cavalier T, Schänzer W. Mass spectrometric characterization of a prolyl hydroxylase inhibitor GSK1278863, its bishydroxylated metabolite, and its implementation into routine doping controls.. Drug Test Anal 2016 Aug;8(8):858-63.
    doi: 10.1002/dta.1870pubmed: 26361079google scholar: lookup
  25. 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 implementation into routine doping controls.. Drug Test Anal 2017 Jan;9(1):61-67.
    doi: 10.1002/dta.2011pubmed: 27346747google scholar: lookup
  26. Eichner D, Van Wagoner RM, Brenner M, Chou J, Leigh S, Wright LR, Flippin LA, 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 Nov;9(11-12):1768-1778.
    doi: 10.1002/dta.2202pubmed: 28378453google scholar: lookup
  27. 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 Mar 20;121:181-187.
    doi: 10.1016/j.jpba.2016.01.029pubmed: 26808067google scholar: lookup
  28. Mikhail E, Siccardi E, Bawazir A, Rajesh A, Prathyush S, Al Wazani DMK, Sabeek M, John T. A validated method for the quantification of IOX-2, a potent prolyl hydroxylase inhibitor in equine urine and plasma using liquid chromatography-high-resolution mass spectrometry.. Drug Test Anal 2021 Jun;13(6):1178-1190.
    doi: 10.1002/dta.3010pubmed: 33533201google scholar: lookup
  29. Mathew B, Philip M, Perwad Z, Karatt TK, Caveney MR, Subhahar MB, Karakka Kal AK. Identification of Hypoxia-inducible factor (HIF) stabilizer roxadustat and its possible metabolites in thoroughbred horses for doping control.. Drug Test Anal 2021 Jun;13(6):1203-1215.
    doi: 10.1002/dta.3014pubmed: 33569900google scholar: lookup
  30. Ishii H, Shibuya M, So YM, Wong JKY, Ho ENM, Kusano K, Sone Y, Kamiya T, Wakuno A, Ito H, Miyata K, Yamada M, Leung GN. Comprehensive metabolic study of IOX4 in equine urine and plasma using liquid chromatography/electrospray ionization Q Exactive high-resolution mass spectrometer for the purpose of doping control.. Drug Test Anal 2022 Feb;14(2):233-251.
    doi: 10.1002/dta.3172pubmed: 34612014google scholar: lookup
  31. Ishii H, Shibuya M, So YM, Wong JKY, Ho ENM, Kusano K, Sone Y, Kamiya T, Wakuno A, Ito H, Miyata K, Yamada M, Leung GN. Long-term monitoring of IOX4 in horse hair and its longitudinal distribution with segmental analysis using liquid chromatography/electrospray ionization Q Exactive high-resolution mass spectrometry for the purpose of doping control.. Drug Test Anal 2022 Jul;14(7):1244-1254.
    doi: 10.1002/dta.3172pubmed: 35195358google scholar: lookup
  32. Philip M, Mathew B, Karatt TK, Perwad Z, Subhahar MB, Karakka Kal AK. Metabolic studies of hypoxia-inducible factor stabilisers IOX2, IOX3 and IOX4 (in vitro) for doping control.. Drug Test Anal 2021 Apr;13(4):794-816.
    doi: 10.1002/dta.3000pubmed: 33458935google scholar: lookup
  33. Philip M, Karakka Kal AK, Subhahar MB, Karatt TK, Mathew B, Perwad Z. In vitro studies of hypoxia inducible factor-prolyl hydroxylase inhibitors daprodustat, desidustat, and vadadustat for equine doping control.. Drug Test Anal 2022 Feb;14(2):317-348.
    doi: 10.1002/dta.3188pubmed: 34714596google scholar: lookup
  34. Pharmaceuticals and Medical Devices Agency. Assessment report for VAFSEO tablet 150 mg and 300 mg (in Japanese). (Accessed on: March 3, 2022).
  35. 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 Nov;30(11):1882-1886.
    doi: 10.1002/bmc.3743pubmed: 27078498google scholar: lookup
  36. 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):356-9.
    doi: 10.1248/cpb.c15-00741pubmed: 27039832google scholar: lookup
  37. 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.
    doi: 10.15583/jpchrom.2017.004google scholar: lookup
  38. 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 Jun;32(6):e4184.
    doi: 10.1002/bmc.4184pubmed: 29283445google scholar: lookup
  39. 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 Aug;35(8):e5124.
    doi: 10.1002/bmc.5124pubmed: 33772839google scholar: lookup
  40. 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 Jul;35(7):e5094.
    doi: 10.1002/bmc.5094pubmed: 33599311google scholar: lookup
  41. Maekawa M, Mano N. Cutting-edge LC-MS/MS applications in clinical mass spectrometry: Focusing on analysis of drugs and metabolites.. Biomed Chromatogr 2022 May;36(5):e5347.
    doi: 10.1002/bmc.5347pubmed: 35073598google scholar: lookup
  42. Ishii H, Shibuya M, Leung GN, Yamashita S, Yamada M, Kushiro A, Kasashima Y, Okada J, Kawasaki K, Kijima-Suda I. Metabolic 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 Mar 13;35(5):e9028.
    doi: 10.1002/rcm.9028pubmed: 33319421google scholar: lookup
  43. Kuuranne T, Vahermo M, Leinonen A, Kostianen R. Electrospray and atmospheric pressure chemical ionization tandem mass spectrometric behavior of eight anabolic steroid glucuronides.. J Am Soc Mass Spectrom 2000 Aug;11(8):722-30.
    doi: 10.1016/S1044-0305(00)00135-5pubmed: 10937795google scholar: lookup
  44. Ward L.C., McCue H.V., Carnell A.J.. Carboxyl methyltransferases: Natural functions and potential applications in industrial biotechnology. ChemCatChem 2021,13,121-128.
    doi: 10.1002/cctc.202001316google scholar: lookup
  45. O'Tuathaigh CM, Desbonnet L, Lee P, Waddington JL. Catechol-O-methyl transferase as a drug target for schizophrenia.. CNS Neurol Disord Drug Targets 2012 May;11(3):282-91.
    doi: 10.2174/187152712800672418pubmed: 22483298google scholar: lookup
  46. Pathania S, Bhatia R, Baldi A, Singh R, Rawal RK. Drug metabolizing enzymes and their inhibitors' role in cancer resistance.. Biomed Pharmacother 2018 Sep;105:53-65.
    doi: 10.1016/j.biopha.2018.05.117pubmed: 29843045google scholar: lookup
  47. Iyamu ID, Huang R. Mechanisms and inhibitors of nicotinamide N-methyltransferase.. RSC Med Chem 2021 Aug 18;12(8):1254-1261.
    doi: 10.1039/D1MD00016Kpubmed: 34458733google scholar: lookup
  48. Conery AR, Rocnik JL, Trojer P. Small molecule targeting of chromatin writers in cancer.. Nat Chem Biol 2022 Feb;18(2):124-133.
    doi: 10.1038/s41589-021-00920-5pubmed: 34952934google scholar: lookup
  49. Wang LL, Ren XX, He Y, Cui GF, Wei ZW, Jia J, Cao J, Liu Y, Cong B, Niu Y, Yun KM. Study on the Pharmacokinetics of Diazepam and Its Metabolites in Blood of Chinese People.. Eur J Drug Metab Pharmacokinet 2020 Aug;45(4):477-485.
    doi: 10.1007/s13318-020-00614-8pubmed: 32219697google scholar: lookup
  50. Wen Z, Tallman MN, Ali SY, Smith PC. UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics.. Drug Metab Dispos 2007 Mar;35(3):371-80.
    doi: 10.1124/dmd.106.012732pubmed: 17151191google scholar: lookup
  51. Ishii H, Leung GN, Yamashita S, Nagata SI, 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 Feb 1;1190:123100.
    doi: 10.1016/j.jchromb.2022.123100pubmed: 35032890google scholar: lookup
  52. Ishii H, Leung GN, Yamashita S, Nagata SI, 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 May;14(5):902-914.
    doi: 10.1002/dta.3242pubmed: 35195357google scholar: lookup
  53. Schebb NH, Franze B, Maul R, Ranganathan A, Hammock BD. In vitro glucuronidation of the antibacterial triclocarban and its oxidative metabolites.. Drug Metab Dispos 2012 Jan;40(1):25-31.
    doi: 10.1124/dmd.111.042283pubmed: 21953915google scholar: lookup
  54. 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 Aug;44(8):677-86.
    doi: 10.3109/00498254.2014.894219pubmed: 24575896google scholar: lookup
  55. Hammond TG, Meng X, Jenkins RE, Maggs JL, Castelazo AS, Regan SL, Bennett SN, Earnshaw CJ, Aithal GP, Pande I, Kenna JG, Stachulski AV, Park BK, Williams DP. 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 Aug;350(2):387-402.
    doi: 10.1124/jpet.114.215079pubmed: 24902585google scholar: lookup
  56. Ebner T, Heinzel G, Prox A, Beschke K, Wachsmuth H. Disposition and chemical stability of telmisartan 1-O-acylglucuronide.. Drug Metab Dispos 1999 Oct;27(10):1143-9.
    pubmed: 10497140
  57. Di Meo F, Steel M, Nicolas P, Marquet P, Duroux JL, Trouillas P. Acylglucuronide in alkaline conditions: migration vs. hydrolysis.. J Mol Model 2013 Jun;19(6):2423-32.
    doi: 10.1007/s00894-013-1790-3pubmed: 23420401google scholar: lookup
  58. Pedersen LC, Yi M, Pedersen LG, Kaminski AM. From Steroid and Drug Metabolism to Glycobiology, Using Sulfotransferase Structures to Understand and Tailor Function.. Drug Metab Dispos 2022 Jul;50(7):1027-1041.
    doi: 10.1124/dmd.121.000478pubmed: 35197313google scholar: lookup
  59. 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 Aug;20(8):828-33.
    doi: 10.1248/bpb.20.828pubmed: 9300125google scholar: lookup
  60. 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 Jul;24(7):759-67.
    doi: 10.1002/bmc.1360pubmed: 20014146google scholar: lookup
  61. Dieterle W, Faigle JW, Küng W, Theobald W. The metabolic fate of 14C-oxaprotiline X HCl in man. III. Stereospecific disposition.. Biopharm Drug Dispos 1984 Oct-Dec;5(4):377-86.
    doi: 10.1002/bdd.2510050408pubmed: 6525444google scholar: lookup
  62. Dębski H, Wiczkowski W, Horbowicz M. Effect of Elicitation with Iron Chelate and Sodium Metasilicate on Phenolic Compounds in Legume Sprouts.. Molecules 2021 Mar 3;26(5).
    doi: 10.3390/molecules26051345pubmed: 33802449google scholar: lookup
  63. Basiliere S, Kerrigan S. Temperature and pH-Dependent Stability of Mitragyna Alkaloids.. J Anal Toxicol 2020 May 18;44(4):314-324.
    doi: 10.1093/jat/bkz103pubmed: 31897484google scholar: lookup
  64. Li J, Ni G, Liu Y, Wang R, Yu D. Long-chain fatty acid acylated derivatives of isoflavone glycosides from the rhizomes of Iris domestica.. Phytochemistry 2022 Jan;193:112977.
    doi: 10.1016/j.phytochem.2021.112977pubmed: 34715401google scholar: lookup
  65. Shimokawa S, Iwashina T, Murakami N. Flower color changes in three Japanese hibiscus species: further quantitative variation of anthocyanin and flavonols.. Nat Prod Commun 2015 Mar;10(3):451-2.
    doi: 10.1177/1934578X1501000319pubmed: 25924527google scholar: lookup
  66. Takeda A, Nakata M, Kijima-Suda I, Tanaka H. 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 .
  67. Ishii H, Leung GN, 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 Dec 15;34(23):e8920.
    doi: 10.1002/rcm.8920pubmed: 32776613google scholar: lookup
  68. Ishii H, Shibuya M, Leung GN, 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 chromatography/high-resolution mass spectrometry.. Rapid Commun Mass Spectrom 2021 Apr 30;35(8):e9050.
    doi: 10.1002/rcm.9050pubmed: 33470485google scholar: lookup
  69. Al-Rifai Z, Mulvey D. Principles of total intravenous anaesthesia: Basic pharmacokinetics and model descriptions. BJA Educ 2016,16,92-97.
    doi: 10.1093/bjaceaccp/mkv021google scholar: lookup

Citations

This article has been cited 2 times.
  1. Oliveira JA, Loria F, Schobinger C, Kuuranne T, Mumenthaler C, Leuenberger N. Comparison between standard hematological parameters and blood doping biomarkers in dried blood spots within the athlete population of Swiss Sport Integrity. Front Sports Act Living 2024;6:1452079.
    doi: 10.3389/fspor.2024.1452079pubmed: 39364095google scholar: lookup
  2. Ishii H, Shigematsu R, Takemoto S, Ishikawa Y, Mizobe F, Nomura M, Arima D, Kunii H, Yuasa R, Yamanaka T, Tanabe S, Nagata SI, Yamada M, Leung GN. Quantification of osilodrostat in horse urine using LC/ESI-HRMS to establish an elimination profile for doping control. Bioanalysis 2024;16(17-18):947-958.
    doi: 10.1080/17576180.2024.2385848pubmed: 39235065google scholar: lookup
Subscribe to our newsletter
Join 99,727 horse owners like you who receive our email updates on horse health and nutrition.