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Perspective

Looking Back Through the MIST: A Perspective of Evolving Strategies and Key Focus Areas for Metabolite Safety Analysis

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Pages 1235-1248 | Published online: 13 Jul 2010

Bibliography

  • Clarke NJ , RingdenD, KorfmacherWA, CoxKA. Systematic LC/MS metabolite identification in drug discovery. Anal. Chem. 73, 430A–439A (2001).
  • Korfmacher WA , BryantMS, CoxKAet al. Strategies for optimising the use of mass spectrometry for drug metabolism participation in new drug discovery. Adv. Mass Spectrom. 15, 679–680 (2001).
  • Kostainien R , KotiahoT, KuuranneT, AuriolaS. Liquid chromatography/atmospheric pressure ionisation–mass spectrometry in drug metabolism studies. J. Mass Spectrom. 38, 357–372 (2003).
  • Watt AP , Mortishire-SmithRJ, GerhardU, ThomasT. Metabolite identification in drug discovery. Drug Discov. Dev. 6, 57–65 (2003).
  • Baillie TA , CayenMN, FoudaHet al. Drug metabolites in safety testing. Toxicol. Appl. Pharmacol. 182, 188–196 (2002).
  • Hastings KL , El-HageJ, JacobsA, LeightonJ, MorseD, OsterbergRE. Letter to the Editor. Toxicol. Appl. Pharmacol. 190, 91–92 (2003).
  • Baillie TA , CayenMN, FoudaHet al. Letter to the Editor. Reply. Toxicol. Appl. Pharmacol. 190, 93–94 (2003).
  • Smith DA , ObachRS. Seeing through the mist: abundance versus percentage. Commentary on metabolites in safety testing. Drug Metab. Dispos. 33, 1409–1417 (2005).
  • Smith DA , ObachRS. Metabolites and safety: what are the concerns and how should we address them? Chem. Res. Toxicol. 19, 1570–1579 (2006).
  • Prueksaritanont T , LinJH, BaillieT. Complicating factors in safety testing of drug metabolites: kinetic differences between generated and preformed metabolites. Toxicol. Appl. Pharmacol. 217, 143–152 (2006).
  • Guengerich FP . Safety assessment of stable drug metabolites. Chem. Res. Toxicol. 19, 1559–1560 (2006).
  • Humphreys WG , UngerSE. Safety assessment of drug metabolites: characterisation of chemically stable metabolites. Chem. Res. Toxicol. 19, 1564–1569 (2006).
  • Prakash C , SharmaR, GleaveM, NeddermanANR. In vitro screening techniques for reactive metabolites for minimizing bioactivation potential in drug discovery. Curr. Drug Metab. 9, 952–964 (2008).
  • Kumar S , KasshunK, Tschirret-GuthRA, MitreK, BaillieT. Minimizing metabolic activation during pharmaceutical lead optimization: progress, knowledge gaps and future directions. Curr. Opin. Drug Discov. Dev. 11, 43–52 (2008).
  • Baillie T . Metabolism and toxicity of drugs. Two decades of progress in industrial drug metabolism. Chem. Res. Toxicol. 21, 129–137 (2008).
  • Walker D , BradyJ, DalvieDet al. A holistic strategy for characterizing the safety of metabolites through drug discovery and development. Chem. Res. Toxicol. 22, 1653–1662 (2009).
  • Nedderman ANR . Metabolites in safety testing: metabolite identification strategies in discovery and development. Biopharm. Drug Dispos. 30, 153–162 (2009).
  • Lappin G , StevensL. Biomedical accelerator mass spectrometry: recent applications in metabolism and pharmacokinetics. Exp. Opin. Drug Metabol. Toxicol. 4, 1021–1033 (2008).
  • Seymour M . The best model for humans is human – how to accelerate early drug development safely. Altern. Lab Anim. 37, 61–65 (2009)
  • Leclerq L , CuyckensF, MannensGSJ, de Vries R, Timmerman P, Evans DC. Which metabolites have we MIST? Retrospective analysis, practical aspects and perspectives for metabolite identification and quantification in pharmaceutical development. Chem. Res. Toxicol. 22, 280–293 (2009).
  • Baillie TA . Approaches to the assessment of stable and chemically reactive drug metabolites in early clinical trials. Chem. Res. Toxicol. 22, 263–266 (2009)
  • Zhu M , ZhangD, ZhangH, ShyuWC. Integrated strategies for assessment of metabolite exposure in humans during drug development: analytical challenges and clinical development considerations. Biopharm. Drug Dispos. 20, 163–184 (2009).
  • Zhuang H , ZhangD, RayK. A software filter to remove interference ions from drug metabolites in accurate mass liquid chromatography/mass spectrometric analyses. J. Mass Spectrom. 38, 1110–1112 (2003).
  • Zhu P , TongW, AltonK, ChowdhuryS. An accurate-mass-based spectral-averaging isotope-pattern-filtering algorithm for extraction of drug metabolites possessing a distinct isotope pattern from LC–MS data. Anal. Chem. 81, 5910–5917 (2009).
  • Wishart DS . Applications of metabolomics in drug discovery and development. Drugs RD9, 307–322 (2008).
  • Alex A , HarveyS, ParsonsT, PullenFS, WrightP, RileyJ-A. Can density functional theory (DFT) be used as an aid to a deeper understanding of tandem mass spectrometric fragmentation pathways? Rapid Commun. Mass Spectrom. 23, 2619–2627 (2009).
  • Dear GJ , JamesAD, SardaS. Ultra-performance liquid chromatography coupled to linear ion trap mass spectrometry for the identification of drug metabolites in biological samples. Rapid Commun. Mass Spectrom. 20, 1351–1360 (2006).
  • Mukhopadhyay R . IMS/MS: its time has come. Anal. Chem. 80, 7918–7920 (2008).
  • Lundahl A , LennernaesH, KnutsonL, BondessonU, HedelandM. Identification of finasteride metabolites in human bile and urine by high-performance liquid chromatography/tandem mass spectrometry. Drug Metab. Dispos. 37, 2008–2017 (2009).
  • Hino F , DolphinD. The biomimetic oxidation of dieldrin using polyhalogenated metalloporphyrins. Chem. Commun. (Camb.). 7, 629–630 (1999).
  • Akagah B , LormierAT, FournetA, FigadereB. Oxidatin of antiparasitic 2-substituted quinolines using metalloporphyrin catalysts: scale-up of a biomimetic reaction for metabolite production of drug candidates. Org. Biomol. Chem. 6, 4494–4497 (2008).
  • Li W , RozzellD, KambourakisS, MayhewM. Biosynthesis of drug metabolites. Biocatal. Pharm. Ind. 183–211 (2009).
  • Tahara K , NishikawaT, HattoriY, LijimaS, KounoY, AbeY. Production of a reactive metabolite of troglitazone by electrochemical oxidation performed in nonaqueous medium. J. Pharm. Biomed. Anal. 50, 1030–1036 (2009).
  • Johansson T , JurvaU, GroenbergG, WeidolfL, MasimirembwaC. Novel metabolites of amodiaquine formed by CYP1A1 and CYP1B1: structure elucidation using electrochemistry, mass spectrometry and NMR. Drug Metab. Dispos. 37, 571–579 (2009).
  • De Boer AR , LetzelT, Van Elswijk DA, Lingeman H, Niessen WMA, Irth H. On-line coupling of high-performance liquid chromatography to a continuous-flow enzyme assay based on electrospray ionization mass spectrometry. Anal. Chem. 76, 3155–3161 (2004).
  • De Boer AR , Alcaide-HidalgoJM, KrabbeJGet al. High-temperature liquid chromatography coupled on-line to a continuous-flow biochemical screening assay with electrospray ionization mass spectrometric detection. Anal. Chem. 77, 7894–7900 (2005).
  • Van Liempd SM , KoolJ, NiessenWMA, van Elswijk DE, Irth H, Vermeulen NPE. On-line formation, separation, and estrogen receptor affinity screening of cytochrome P450-derived metabolites of selective estrogen receptor modulators. Drug Metab. Dispos. 34, 1640–1649 (2006).
  • Van Liempd SM , KoolJ, MeermanJH, IrthH, VermeulenNP. Metabolic profiling of endocrine-disrupting compounds by on-line cytochrome P450 bioreaction coupled to on-line receptor affinity screening. Chem. Res. Toxicol. 20, 1825–1832 (2007).
  • De Vlieger JSB , KolkmanAJ, AmptKAMet al. Determination and identification of estrogenic compounds generated with biosynthetic enzymes using hyphenated screening assays, high resolution mass spectrometry and off-line NMR. J. Chromatogr. B878, 667–674 (20010).
  • Wright P , MiaoZ, ShillidayB. Metabolite quantitation: detector technology and MIST implications. Bioanalysis1, 831–845 (2009).
  • Císař P , NobilisM, VybíralováZet al. Disposition study of a new potential antineoplastic agent dimefluron in rats using high-performance liquid chromatography with ultraviolet and mass spectrometric detection. J. Pharm. Biomed. Anal. 37, 1059–1071 (2005).
  • Vishwanathan K , BabalolaK, WangJet al. Obtaining exposures of metabolites in preclinical species through plasma pooling and quantitative NMR: addressing metabolites in safety testing (MIST) guidance without using radiolabeled compounds and chemically synthesized metabolite standards. Chem. Res. Toxicol. 2, 311–322 (2009).
  • Martino R , GilardV, DesmoulinF, Malet-MartinoM. Fluorine-19 or phosphorus-31 NMR spectroscopy: a suitable analytical technique for quantitative In vitro metabolic studies of fluorinated or phosphorylated drugs. J. Pharm. Biomed. Anal. 38, 871–891 (2005).
  • Espina R , YuL, WangJet al. Nuclear magnetic resonance spectroscopy as a quantitative tool to determine the concentrations of biologically produced metabolites: implications in metabolites in safety testing. Chem. Res. Toxicol. 22, 299–310 (2009).
  • Dear GJ , RobertsAD, BeaumontC, NorthSE. Evaluation of preparative high performance liquid chromatography and cryoprobe–nuclear magnetic resonance spectroscopy for the early quantitative estimation of drug metabolites in human plasma. J. Chromatogr. B876, 182–190 (2008).
  • Skordi E , WilsonID, LindonJC, NicholsonJK. Characterization and quantification of metabolites of racemic ketoprofen excreted in urine following oral administration to man by 1H-NMR spectroscopy, directly coupled HPLC-MS and HPLC-NMR, and circular dichroism. Xenobiotica34, 1075–1089 (2004).
  • Walker GS , O’ConnellTN. Comparison of LC-NMR and conventional NMR for structure elucidation in drug metabolism studies. Exp. Opin. Drug Metab. Toxicol. 4, 1295–1305 (2008).
  • Godejohann M , Tseng L-H, Braumann U, Fuchser J, Spraul M. Characterization of a paracetamol metabolite using on-line LC–SPE–NMR–MS and a cryogenic NMR probe. J. Chromatogr. A1058, 191–196 (2004).
  • Corcoran O , SpraulM. LC-NMR-MS in drug discovery. Drug Discovery Today 8, 624–631 (2004).
  • Emwas A-H , SaundersM, LudwigC, GuentherUL. Determinants for optimal enhancement in ex site DNP experiments. Appl. Magn. Reson. 34, 483–494 (2008).
  • Roth M , BargonJ, SpiessHW, KochA. Parahydrogen induced polarization of barbituric acid derivatives: 1H hyperpolarization studies. Magn. Reson. Chem. 48, 713–717 (2008).
  • Wishart DS . Quantitative metabolomics using NMR. Trends Anal. Chem. 27, 228–237 (2008).
  • Reynolds G , WilsonM, PeetA, ArvanitisTN. An algorithm for the automated quantitation of metabolites in In vitro signals. Magn. Reson. Med. 56, 1211–1219 (2006).
  • Gammelgaard B , HansenHR, SturupS, MollerC. The use of inductively coupled plasma mass spectrometry in drug metabolism studies. Exp. Opin. Drug Metab. Toxicol. 4, 1187–1207 (2008).
  • Smith C , JensenBP, WilsonID, Abou-ShakraF, CrowtherD. High-performance liquid chromatography/inductively coupled plasma mass spectrometry and tandem mass spectrometry for the detection of carbon containing compounds. Rapid Commun. Mass Spectrom. 18, 1487–1492 (2004).
  • Jensen BP , SmithC, WilsonID, WeidolfL. Sensitive sulphur-specific detection of omeprazole metabolites in rat urine by high-performance liquid chromatography/inductively coupled plasma mass spectrometry. Rapid Commun. Mass Spectrom. 18, 181–183 (2004).
  • Duckett CJ , LindonJC, WalkerH, Abou-ShakraF, WilsonID, NicholsonJK. Metabolism of 3-chloro-4-fluoroaniline in rat using [14C]-radio labelling, 19F-NMR spectroscopy, HPLC–MS/MS, HPLC–ICPMS and HPLC–NMR. Xenobiotica36, 59–77 (2006).
  • Jensen BP , GammelgaardB, HansenSH, AndersenJV. HPLC–ICP–MS compared with radiochemical detection for metabolite profiling of 3H-bromahexine in rat urine and faeces. J. Anal. At. Spectrom. 20, 204–209 (2005).
  • Duckett CJ , BaileyNJC, WalkerHet al. Quantitation in gradient high performance liquid chromatography/inductively coupled mass spectrometry investigated using diclofenac and chloroprozamine. Rapid Commun. Mass Spectrom. 16, 245–247 (2002).
  • De Wolf K , BalcaenL, Van de Walle E, Cuyckens F, Vanhaecke F. A comparison between HPLC–dynamic reaction cell–ICP–MS and HPLC–sector field–ICP–MS for the detection of glutathione-trapped reactive drug metabolites using clozapine as a model compound. J. Anal. At. Spectrom. 25, 419–425 (20010).
  • Vogel JS , TurteltaubKW. Bioanalytical application of accelerator mass spectrometry for pharmaceutical research. Curr. Pharm. Des. 6, 991–2007 (2000).
  • Garner RC . Accelerator mass spectrometry in pharmaceutical research and development – a new ultrasensitive analytical method for isotope measurement. Curr. Drug Metab. 1, 205–230 (2000).
  • Buchholz BA , DuekerSR, LinY, CliffordAJ, VogelJS. Methods and application of HPLC–AMS. Nucl. Instrum. Methods Phys. Res. B. 172, 910–914 (2000).
  • Barker J , GarnerRC. Biomedical applications of accelerator mass spectrometry–isotope measurements at the level of the atom. Rapid Commun. Mass Spectrom. 13, 285–293 (1999).
  • Garner RC . Less is more: the human microdosing concept. Drug Discovery Today10, 449–451 (2005).
  • Garner RC , GorisI, LaenenAAEet al. Evaluation of accelerator mass spectrometry in a human mass balance and pharmacokinetic study – experience with 14C-labelled (R)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone (R115777), a farnesyl transferase inhibitor. Drug Metab. Dispos. 30, 823–830 (2002).
  • Smith DA , ObachRS. Metabolites in Safety Testing (MIST): considerations of mechanisms of toxicity with dose, abundance, and duration of treatment. Chem. Res. Toxicol. 22, 267–279 (2009).
  • Martignoni M , GroothuisGM, De Kanter R. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Exp. Opin. Drug Metabol. Toxicol. 2, 875–894 (2006).
  • Zuber R , AnzenbacherovaE, AnzenbacherP. Cytochromes P450 and experimental models of drug metabolism. J. Cell. Mol. Med. 6, 189–198 (2002).
  • Breyer-Pfaff U , WachsmuthH. Tertiary N-glucuronides of clozapine and its metabolite desmethylclozapine in patient urine. Drug Metab. Dispos. 29, 1343–1348 (2001).
  • Klieber S , HuglaS, NgoRet al. Contribution of the N-glucuronidation pathway to the overall In vitro metabolic clearance of midazolam in humans. Drug Metab. Dispos. 36, 851–862 (2008).
  • Kaye B , OffermanJL, ReidJL, ElliottHL, HillisWS. A species difference in the presystemic metabolism of carbazeran in dog and man. Xenobiotica14, 935–945 (1984)
  • Kaye B , RanceDJ, WaringL. Oxidative metabolism of carbazeran In vitro by liver cytosol of baboon and man. Xenobiotica15, 237–242 (1985).
  • Bruck M , LiQ, LamgJG, TukeyRH. Characterisation of rabbit UDP-glucuronosyltransferase UGT1A7: tertiary amine glucuronidation is catalysed by UGT1A7 and UGT1A4. Arch. Biochem. Biophys. 348, 357–364 (1997).
  • Sugihara K , KitamuraS, TatsumiK. Strain differences of liver aldehyde oxidase activity in rats. Biochem. Mol. Biol. Int. 37, 861–869 (1995).
  • Abel S , RussellD, WhitlockLA, RidgwayCE, NeddermanANR, WalkerDK. Assessment of the absorption, metabolism and absolute bioavailability of maraviroc in healthy male subjects. Br. J. Clin. Pharmacol. 65, 60–67 (2008).
  • Walker DK , AbelS, CombyP, MuirheadGJ, NeddermanANR, SmithDA. Species differences in the disposition of the CCR5 antagonist, UK-427,857, a new potential treatment for HIV. Drug Metab. Dispos. 33, 587–595 (2005).
  • Vourvahis M , GleaveM, NeddermanANRet al. Excretion and metabolism of lersivirine (UK-453,061), a next-generation NNRTI, following administration of [14C] lersivirine to healthy volunteers. Drug Metab. Dispos. DOI: 10.1124/dmd.109.031252 (In Press).
  • Atrakchi AH . Interpretation and considerations on the safety evaluation of human drug metabolites. Chem. Res. Toxicol. 22, 1217–1220 (2009).
  • Robison TW , JacobsA. Metabolites in safety testing. Bioanalysis1, 1193–1200 (2009).

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