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Review

Review on In Vivo Profiling of Drug Metabolites with Lc-Ms/Ms in the Past Decade

, & ORCID Icon
Pages 1697-1722 | Received 29 Jun 2021, Accepted 13 Oct 2021, Published online: 26 Oct 2021

References

  • Nalbantoglu S . Metabolomics: Basic principles and strategies. Mol. Med.IntechOpenDOI: 10.5772/intechopen.88563 (2019). https://www.intechopen.com/chapters/68486
  • Bowen BP , NorthenTR. Dealing with the unknown: metabolomics and metabolite atlases. J. Am. Soc. Mass Spectrom.21(9), 1471–1476 (2010).
  • Kwak M , KangK, WangY. Methods of metabolite identification using MS/MS data. J. Comput. Inf. Syst.1–7 https://doi.org/10.1080/08874417.2019.1681328 (2019).
  • Pauling L , RobinsonAB, TeranishiR, CaryP. Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography. Proc. Natl Acad. Sci. USA68(10), 2374–2376 (1971).
  • Horning EC , HorningM-G. Metabolic profiles: gas-phase methods for analysis of metabolites. Clin. Chem.17(8), 802–809 (1971).
  • Oliver SG , WinsonMK, KellDB, BaganzF. Systematic functional analysis of the yeast genome. Trends Biotechnol.16(9), 373–378 (1998).
  • Zhang Z , ZhuM, TangW. Metabolite identification and profiling in drug design: current practice and future directions. Curr. Pharm. Des.15(19), 2220–2235 (2009).
  • Prasad B , GargA, TakwaniH, SinghS. Metabolite identification by liquid chromatography-mass spectrometry. Trends Anal. Chem.30(2), 360–387 (2011).
  • Xiao JF , ZhouB, RessomHW. Metabolite identification and quantitation in LC-MS/MS-based metabolomics. Trends Anal. Chem.32, 1–14 (2012).
  • Roessner U , BowneJ. What is metabolomics all about?BioTechniques46(5), 363–365 (2009).
  • Want EJ , CravattBF, SiuzdakG. The expanding role of mass spectrometry in metabolite profiling and characterization. Chembiochem6(11), 1941–1951 (2005).
  • Muhamad N , Na-BangchangK. Metabolite profiling in anticancer drug development: a systematic review. Drug Des. Devel. Ther.14, 1401 (2020).
  • Clarke NJ , RindgenD, KorfmacherWA, CoxKA. Peer reviewed: systematic LC/MS metabolite identification in drug discovery. Anal. Chem.73(15), 430 A–439 A (2001).
  • Paul W , SteinwedelH. A new mass spectrometer without a magnetic field. Zeitschrift fuer Naturforschung (West Germany) Divided into Z. Nautrforsch., A, and Z. Naturforsch., B: Anorg. Chem., Org. Chem., Biochem., Biophys.8 (1953).
  • Perchalski RJ , YostRA, WilderB. Structural elucidation of drug metabolites by triple-quadrupole mass spectrometry. Anal. Chem.54(9), 1466–1471 (1982).
  • Lee MS , YostRA. Rapid identification of drug metabolites with tandem mass spectrometry. Biomed. Environ. Mass Spectrom.15(4), 193–204 (1988).
  • Bateman KP , Castro-PerezJ, WronaMet al. MSE with mass defect filtering for in vitro and in vivo metabolite identification. Rapid Commun. Mass Spectrom.21(9), 1485–1496 (2007).
  • Gajula SNR , NadimpalliN, SontiR. Drug metabolic stability in early drug discovery to develop potential lead compounds. Drug Metab. Rev. ( just-accepted), 1–47 (2021).
  • Lu D , ZhangS, WangDet al. Identification of flurochloridone metabolites in rat urine using liquid chromatography/high resolution mass spectrometry. J. Chromatogr. A1445, 80–92 (2016).
  • Lei Z , HuhmanDV, SumnerLW. Mass spectrometry strategies in metabolomics. J. Biol. Chem.286(29), 25435–25442 (2011).
  • Theodoridis GA , GikaHG, WantEJ, WilsonID. Liquid chromatography–mass spectrometry based global metabolite profiling: a review. Anal. Chim. Acta711, 7–16 (2012).
  • Beckonert O , KeunHC, EbbelsTMet al. Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat. Protoc.2(11), 2692–2703 (2007).
  • Dunn WB , EllisDI. Metabolomics: current analytical platforms and methodologies. Trends Anal. Chem.24(4), 285–294 (2005).
  • Dunn WB , BroadhurstD, BegleyPet al. Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nat. Protoc.6(7), 1060–1083 (2011).
  • Vuckovic D . Current trends and challenges in sample preparation for global metabolomics using liquid chromatography–mass spectrometry. Anal. Bioanal. Chem.403(6), 1523–1548 (2012).
  • Zhang Q-H , ZhouL-D, ChenH, WangC-Z, XiaZ-N, YuanC-S. Solid-phase microextraction technology for in vitro and in vivo metabolite analysis. Trends Anal. Chem.80, 57–65 (2016).
  • Navitha Reddy G , DilipZagade A, SenguptaP. Current direction and advances in analytical sample extraction techniques for drugs with special emphasis on bioanalysis. Bioanalysis11(04), 313–332 (2019).
  • Gao D , WangD-D, ZhangQet al. In vivo selective capture and rapid identification of luteolin and its metabolites in rat livers by molecularly imprinted solid-phase microextraction. J. Agric. Food Chem.65(6), 1158–1166 (2017).
  • Simões RA , BonatoPS, MirnaghiFS, BojkoB, PawliszynJ. Bioanalytical method for in vitro metabolism study of repaglinide using 96-blade thin-film solid-phase microextraction and LC–MS/MS. Bioanalysis7(1), 65–77 (2015).
  • Wang C , LiP, LianAet al. Blood volatile compounds as biomarkers for colorectal cancer. Cancer Biol. Ther.15(2), 200–206 (2014).
  • Wang D-D , GaoD, HuangY-K, XuW-J, XiaZ-N. Preparation of restricted access molecularly imprinted polymers based fiber for selective solid-phase microextraction of hesperetin and its metabolites in vivo. Talanta202, 392–401 (2019).
  • Jager NG , RosingH, SchellensJH, BeijnenJH. Procedures and practices for the validation of bioanalytical methods using dried blood spots: a review. Bioanalysis6(18), 2481–2514 (2014).
  • Schänzer W , OpfermannG, DonikeM. Metabolism of stanozolol: identification and synthesis of urinary metabolites. J. Steroid Biochem.36(1–2), 153–174 (1990).
  • Thevis M , FußhöllerG, GeyerHet al. Detection of stanozolol and its major metabolites in human urine by liquid chromatography-tandem mass spectrometry. Chromatographia64(7), 441–446 (2006).
  • Engskog MK , HaglöfJ, ArvidssonT, PetterssonC. LC–MS based global metabolite profiling: the necessity of high data quality. Metabolomics12(7), 114 (2016).
  • Bruce SJ , TavazziI, ParisodVR, RezziS, KochharS, GuyPA. Investigation of human blood plasma sample preparation for performing metabolomics using ultrahigh performance liquid chromatography/mass spectrometry. Anal. Chem.81(9), 3285–3296 (2009).
  • León Z , García-CañaverasJC, DonatoMT, LahozA. Mammalian cell metabolomics: experimental design and sample preparation. Electrophoresis34(19), 2762–2775 (2013).
  • Michopoulos F , LaiL, GikaH, TheodoridisG, WilsonI. UPLC-MS-based analysis of human plasma for metabonomics using solvent precipitation or solid phase extraction. J. Proteome Res.8(4), 2114–2121 (2009).
  • Pereira H , MartinJ-F, JolyC, SébédioJ-L, Pujos-GuillotE. Development and validation of a UPLC/MS method for a nutritional metabolomic study of human plasma. Metabolomics6(2), 207–218 (2010).
  • Rico E , GonzálezO, BlancoME, AlonsoRM. Evaluation of human plasma sample preparation protocols for untargeted metabolic profiles analyzed by UHPLC-ESI-TOF-MS. Anal. Bioanal. Chem.406(29), 7641–7652 (2014).
  • Sarafian MH , GaudinM, LewisMRet al. Objective set of criteria for optimization of sample preparation procedures for ultra-high throughput untargeted blood plasma lipid profiling by ultra performance liquid chromatography–mass spectrometry. Anal. Chem.86(12), 5766–5774 (2014).
  • Tulipani S , LlorachR, Urpi-SardaM, Andres-LacuevaC. Comparative analysis of sample preparation methods to handle the complexity of the blood fluid metabolome: when less is more. Anal. Chem.85(1), 341–348 (2013).
  • Want EJ , WilsonID, GikaHet al. Global metabolic profiling procedures for urine using UPLC–MS. Nat. Protoc.5(6), 1005 (2010).
  • Vorkas PA , IsaacG, AnwarMAet al. Untargeted UPLC-MS profiling pipeline to expand tissue metabolome coverage: application to cardiovascular disease. Anal. Chem.87(8), 4184–4193 (2015).
  • Yu Z , KastenmüllerG, HeYet al. Differences between human plasma and serum metabolite profiles. PLoS ONE6(7), e21230 (2011).
  • Shen Z , KangP, RahavendranSV. Metabolite profiling of dasatinib dosed to Wistar Han rats using automated dried blood spot collection. J. Pharm. Biomed. Anal.67, 92–97 (2012).
  • Tretzel L , ThomasA, PiperTet al. Fully automated determination of nicotine and its major metabolites in whole blood by means of a DBS online-SPE LC-HR-MS/MS approach for sports drug testing. J. Pharm. Biomed. Anal.123, 132–140 (2016).
  • Varkhede NR , JhajraS, AhireDS, SinghS. Metabolite identification studies on amiodarone in in vitro (rat liver microsomes, rat and human liver S9 fractions) and in vivo (rat feces, urine, plasma) matrices by using liquid chromatography with high-resolution mass spectrometry and multiple-stage mass spectrometry: characterization of the diquinone metabolite supposedly responsible for the drug's hepatotoxicity. Rapid Commun. Mass Spectrom.28(4), 311–331 (2014).
  • Patel PN , KalariyaPD, SwamyCV, GananadhamuS, SrinivasR. Quantitation of acotiamide in rat plasma by UHPLC-Q-TOF-MS: method development, validation and application to pharmacokinetics. Biomed. Chromatogr.30(3), 363–368 (2016).
  • Chavan BB , KalariyaPD, TiwariSet al. Identification and characterization of vilazodone metabolites in rats and microsomes by ultrahigh-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry. Rapid Commun. Mass Spectrom.31(23), 1974–1984 (2017).
  • Attwa MW , KadiAA, AlrabiahH, DarwishHW. LC–MS/MS reveals the formation of iminium and quinone methide reactive intermediates in entrectinib metabolism: in vivo and in vitro metabolic investigation. J. Pharm. Biomed. Anal.160, 19–30 (2018).
  • Chavan BB , TiwariS, ShankarGet al. In vitro and in vivo metabolic investigation of the Palbociclib by UHPLC-Q-TOF/MS/MS and in silico toxicity studies of its metabolites. J. Pharm. Biomed. Anal.157, 59–74 (2018).
  • Sun W , NguyenKD, FitchWLet al. In vitro and in vivo metabolite identification of a novel benzimidazole compound ZLN005 by liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass Spectrom.32(6), 480–488 (2018).
  • Stopfer P , MarzinK, NarjesHet al. Afatinib pharmacokinetics and metabolism after oral administration to healthy male volunteers. Cancer Chemother. Pharmacol.69(4), 1051–1061 (2012).
  • Attwa MW , KadiAA, DarwishHW, AmerSM, Al-ShakliahNS. Identification and characterization of in vivo, in vitro and reactive metabolites of vandetanib using LC–ESI–MS/MS. Chem. Cent. J.12(1), 1–16 (2018).
  • Roosendaal J , RosingH, LucasLet al. Mass balance and metabolite profiling of 14 C-guadecitabine in patients with advanced cancer. Invest. New Drugs38(4), 1–11 (2019).
  • Shin S-H , ParkM-H, ByeonJ-Jet al. Analysis of vipadenant and its in vitro and in vivo metabolites via liquid chromatography-quadrupole-time-of-flight mass spectrometry. Pharmaceutics10(4), 260 (2018).
  • Thakkar D , KateAS. Update on metabolism of abemaciclib: in silico, in vitro, and in vivo metabolite identification and characterization using high resolution mass spectrometry. Drug test. Anal.12(3), 331–342 (2020).
  • Zhou L , LiuH, XuZ, GuanS, ZhangL. Identification and structural characterization of febuxostat metabolites in rat serum and urine samples using UHPLC–QTOF/MS. Biomed. Chromatogr.33(9), e4568 (2019).
  • Zhu C , WanM, ChengH, WangH, ZhuM, WuC. Rapid detection and structural characterization of verapamil metabolites in rats by UPLC–MSE and UNIFI platform. Biomed. Chromatogr.34(1), e4702 (2020).
  • Yang J , WangZ, FangYet al. Pharmacokinetics, pharmacodynamics, metabolism, distribution, and excretion of carfilzomib in rats. Drug Metab. Dispos.39(10), 1873–1882 (2011).
  • Yeole RD , RaneVP, AhirraoVKet al. Identification of metabolites of novel Anti-MRSA fluoroquinolone WCK 771 in mouse, rat, rabbit, dog, monkey and human urine using liquid chromatography tandem mass spectrometry. Biomed. Chromatogr.33(7), e4532 (2019).
  • Al-Shakliah NS , AttwaMW, KadiAA, AlrabiahH. Identification and characterization of in silico, in vivo, in vitro, and reactive metabolites of infigratinib using LC-ITMS: bioactivation pathway elucidation and in silico toxicity studies of its metabolites. RSC Advances10(28), 16231–16244 (2020).
  • Tiwari SS , DhimanV, MukeshS, SangamwarAT, SrinivasR, TalluriMK. Identification and characterization of novel metabolites of nintedanib by ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry with in silico toxicological assessment. Rapid Commun. Mass Spectrom.34(22), e8915 (2020).
  • Wang C , ZhangJ, ZhouSet al. Tentative identification of gefitinib metabolites in non-small-cell lung cancer patient plasma using ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry. PLoS ONE15(7), e0236523 (2020).
  • Wójtowicz M , JarekA, ChajewskaK, Turek-LepaE, KwiatkowskaD. Determination of designer doping agent–2-ethylamino-1-phenylbutane–in dietary supplements and excretion study following single oral supplement dose. J. Pharm. Biomed. Anal.115, 523–533 (2015).
  • Rzeppa S , VietL. Analysis of sulfate metabolites of the doping agents oxandrolone and danazol using high performance liquid chromatography coupled to tandem mass spectrometry. J. Chromatogr. B.1029, 1–9 (2016).
  • Ameline A , GheddarL, RaulJ-S, KintzP. Characterization of letrozole in human hair using LC-MS/MS and confirmation by LC-HRMS: application to a doping case. J. Chromatogr. B.1162, 122495 (2021).
  • La Maida N , MannocchiG, GiorgettiR, SirignanoA, RicciG, BusardòFP. Optimization of a rapid sample pretreatment for the quantification of COCAINE and its main metabolites in hair through a new and validated GC-MS/MS method. J. Pharm. Biomed. Anal.204, 114282 (2021).
  • Ma S , ZengZ, LinMet al. PAHs and their hydroxylated metabolites in the human fingernails from e-waste dismantlers: implications for human non-invasive biomonitoring and exposure. Environ. Pollut.283, 117059 (2021).
  • Kim J , ChoH-D, SuhJHet al. Analysis of nicotine metabolites in hair and nails using QuEChERS method followed by liquid chromatography–tandem mass spectrometry. Molecules25(8), 1763 (2020).
  • Wishart DS . Advances in metabolite identification. Bioanalysis3(15), 1769–1782 (2011).
  • Gajula SNR , NanjappanS. Metabolomics: a recent advanced omics technology in herbal medicine research. In: Medicinal and Aromatic Plants. Elsevier, 97–117 (2021).
  • Zhang H , ZhangD, RayK. A software filter to remove interference ions from drug metabolites in accurate mass liquid chromatography/mass spectrometric analyzes. J. Mass Spectrom.38(10), 1110–1112 (2003).
  • Chen L-Z , JungnikA, MaoYet al. Biotransformation and mass balance of the SGLT2 inhibitor empagliflozin in healthy volunteers. Xenobiotica45(6), 520–529 (2015).
  • Picó Y , BlascoC, FontG. Environmental and food applications of LC–tandem mass spectrometry in pesticide-residue analysis: an overview. Mass Spectrom. Rev.23(1), 45–85 (2004).
  • Soler C , MañesJ, PicóY. Comparison of liquid chromatography using triple quadrupole and quadrupole ion trap mass analyzers to determine pesticide residues in oranges. J. Chromatogr. A1067(1–2), 115–125 (2005).
  • Gautam N , LinZ, BanoubMGet al. Simultaneous quantification of intracellular lamivudine and abacavir triphosphate metabolites by LC–MS/MS. J. Pharm. Biomed. Anal.153, 248–259 (2018).
  • Rashid MM , LeeH, JungBH. Metabolite identification and pharmacokinetic profiling of PP242, an ATP-competitive inhibitor of mTOR using ultra high-performance liquid chromatography and mass spectrometry. J. Chromatogr. B.1072, 244–251 (2018).
  • Rousu T , HerttuainenJ, TolonenA. Comparison of triple quadrupole, hybrid linear ion trap triple quadrupole, time-of-flight and LTQ-Orbitrap mass spectrometers in drug discovery phase metabolite screening and identification in vitro–amitriptyline and verapamil as model compounds. Rapid Commun. Mass Spectrom.24(7), 939–957 (2010).
  • Hakala KS , KostiainenR, KetolaRA. Feasibility of different mass spectrometric techniques and programs for automated metabolite profiling of tramadol in human urine. Rapid Commun. Mass Spectrom.20(14), 2081–2090 (2006).
  • Tolonen A , TurpeinenM, PelkonenO. Liquid chromatography–mass spectrometry in in vitro drug metabolite screening. Drug Discov. Today14(3–4), 120–133 (2009).
  • Jemal M , OuyangZ, ZhaoW, ZhuM, WuWW. A strategy for metabolite identification using triple-quadrupole mass spectrometry with enhanced resolution and accurate mass capability. Rapid Commun. Mass Spectrom.17(24), 2732–2740 (2003).
  • Cotter RJ . Time-of-flight mass spectrometry. ACS Publications (1993).
  • Wiley W , MclarenIH. Time-of-flight mass spectrometer with improved resolution. Rev. Sci. Instrum.26(12), 1150–1157 (1955).
  • Glish GL , GoeringerDE. A tandem quadrupole/time-of-flight instrument for mass spectrometry/mass spectrometry. Anal. Chem.56(13), 2291–2295 (1984).
  • El-Aneed A , CohenA, BanoubJ. Mass spectrometry, review of the basics: electrospray, MALDI, and commonly used mass analyzers. Appl. Spectrosc. Rev.44(3), 210–230 (2009).
  • Allen DR , McwhinneyBC. Quadrupole time-of-flight mass spectrometry: a paradigm shift in toxicology screening applications. Clin Biochem Rev40(3), 135 (2019).
  • Kim J , BasiriB, HassanCet al. Metabolite profiling of the antisense oligonucleotide eluforsen using liquid chromatography-mass spectrometry. Mol. Ther. Nucleic Acids17, 714–725 (2019).
  • Vishnuvardhan C , BaikadiS, BorkarRM, SrinivasR, SatheeshkumarN. In vivo metabolic investigation of silodosin using UHPLC–QTOF–MS/MS and in silico toxicological screening of its metabolites. J. Mass Spectrom.51(10), 867–882 (2016).
  • Li X , TangM, WangHet al. In Vitro and In Vivo Primary Metabolic Characterization of F18, a Novel Histone Deacetylase-6 (HDAC6) Inhibitor, Using UHPLC–QqQ–MS/MS and Q-TOF–MS Methods. Chromatographia79(21), 1479–1490 (2016).
  • Tian T , JinY, MaYet al. Identification of metabolites of oridonin in rats with a single run on UPLC-Triple-TOF-MS/MS system based on multiple mass defect filter data acquisition and multiple data processing techniques. J. Chromatogr. B.1006, 80–92 (2015).
  • Ludwig F-A , FischerS, SmitsRet al. Exploring the metabolism of (+)-[18f] flubatine in vitro and in vivo: lc-ms/ms aided identification of radiometabolites in a clinical pet study. Molecules23(2), 464 (2018).
  • Pan H , LiY, HuangL, ZhouX, LuY, ShiF. Development and validation of a rapid LC–MS/MS method for simultaneous quantification of arecoline and its two active metabolites in rat plasma and its application to a pharmacokinetic study. J. Pharm. Biomed. Anal.154, 397–403 (2018).
  • Dunn WB , BroadhurstD, BrownMet al. Metabolic profiling of serum using Ultra Performance Liquid Chromatography and the LTQ-Orbitrap mass spectrometry system. J. Chromatogr. B.871(2), 288–298 (2008).
  • Hu Q , NollRJ, LiH, MakarovA, HardmanM, GrahamCooks R. The Orbitrap: a new mass spectrometer. J. Mass Spectrom.40(4), 430–443 (2005).
  • Pelkonen O , TolonenA, KorjamoT, TurpeinenM, RaunioH. From known knowns to known unknowns: predicting in vivo drug metabolites. Bioanalysis1(2), 393–414 (2009).
  • Nassar A-EF , TalaatRE. Strategies for dealing with metabolite elucidation in drug discovery and development. Drug Discov. Today9(7), 317–327 (2004).
  • Viant MR , BeardenDW, BundyJGet al. International NMR-based environmental metabolomics intercomparison exercise. Environ. Sci. Technol.43(1), 219–225 (2009).
  • Zhang S , GowdaGN, YeT, RafteryD. Advances in NMR-based biofluid analysis and metabolite profiling. Analyst135(7), 1490–1498 (2010).
  • Ye T , MoH, ShanaiahN, GowdaGN, ZhangS, RafteryD. Chemoselective 15N tag for sensitive and high-resolution nuclear magnetic resonance profiling of the carboxyl-containing metabolome. Anal. Chem.81(12), 4882–4888 (2009).
  • Grimes JH , O'connellTM. The application of micro-coil NMR probe technology to metabolomics of urine and serum. J. Biomol. NMR49(3–4), 297–305 (2011).
  • Putzbach K , KruckerM, GrynbaumMD, HentschelP, WebbAG, AlbertK. Hyphenation of capillary high-performance liquid chromatography to microcoil magnetic resonance spectroscopy – determination of various carotenoids in a small-sized spinach sample. J. Pharm. Biomed. Anal.38(5), 910–917 (2005).
  • Polet M , Van EenooP. GC-C-IRMS in routine doping control practice: 3 years of drug testing data, quality control and evolution of the method. Anal. Bioanal. Chem.407(15), 4397–4409 (2015).
  • Looser R , KrotzkyAJ, TretheweyRN. Metabolite profiling with GC-MS and LC-MS. In: Metabolome analyzes: Strategies for Systems Biology.Springer, 103–118 (2005).
  • Zeki ÖC , EylemCC, ReçberT, KırS, NemutluE. Integration of GC-MS and LC-MS for untargeted metabolomics profiling. J. Pharm. Biomed. Anal.113509 (2020).
  • Kopka J . Current challenges and developments in GC–MS based metabolite profiling technology. J. Biotechnol.124(1), 312–322 (2006).
  • Savchuk S , AppolonovaS, PechnikovA, RizvanovaL, ShestakovaK, TagliaroF. In vivo metabolism of the new synthetic cannabinoid APINAC in rats by GC–MS and LC–QTOF-MS. Forensic Toxicol.35(2), 359–368 (2017).
  • Ooms JA , KnegtL, KosterEHM. Exploration of a new concept for automated dried blood spot analysis using flow-through desorption and online SPE–MS/MS. Bioanalysis3(20), 2311–2320 (2011).
  • Hu B , ZhengB, RickertDet al. Direct coupling of solid phase microextraction with electrospray ionization mass spectrometry: a case study for detection of ketamine in urine. Anal. Chim. Acta1075, 112–119 (2019).
  • Ng TT . Rapid determination of drugs-of-abuse in urine and oral fluid and rapid authentication of edible oils by mass spectrometry (2018). https://theses.lib.polyu.edu.hk/handle/200/9596
  • Zhu M , MaL, ZhangDet al. Detection and characterization of metabolites in biological matrices using mass defect filtering of liquid chromatography/high resolution mass spectrometry data. Drug Metab. Dispos.34(10), 1722–1733 (2006).
  • Zhang H , ZhangD, RayK, ZhuM. Mass defect filter technique and its applications to drug metabolite identification by high-resolution mass spectrometry. J. Mass Spectrom.44(7), 999–1016 (2009).
  • Sleno L . The use of mass defect in modern mass spectrometry. J. Mass Spectrom.47(2), 226–236 (2012).
  • Déglon J , ThomasA, DaaliYet al. Automated system for on-line desorption of dried blood spots applied to LC/MS/MS pharmacokinetic study of flurbiprofen and its metabolite. J. Pharm. Biomed. Anal.54(2), 359–367 (2011).
  • Guthrie R . Blood screening for phenylketonuria. JAMA178(8), 863–863 (1961).
  • Mcdade TW , WilliamsS, SnodgrassJJ. What a drop can do: dried blood spots as a minimally invasive method for integrating biomarkers into population-based research. Demography44(4), 899–925 (2007).
  • Vu D , KosterR, BolhuisMet al. Simultaneous determination of rifampicin, clarithromycin and their metabolites in dried blood spots using LC–MS/MS. Talanta121, 9–17 (2014).
  • Sonti R , Hertel-HeringI, LamontanaraAJ, HantschelO, GrzesiekS. ATP site ligands determine the assembly state of the Abelson kinase regulatory core via the activation loop conformation. J. Am. Chem. Soc.140(5), 1863–1869 (2018).
  • Hantschel O , GrebienF, Superti-FurgaG. The growing arsenal of ATP-competitive and allosteric inhibitors of BCR–ABL. Cancer Res.72(19), 4890–4895 (2012).
  • Fiehn O , KindT. Metabolite profiling in blood plasma. In: Metabolomics, Springer ( Eds). 3–17 (2007).
  • Kulkarni P , KaranamA, GurjarMet al. Effect of various anticoagulants on the bioanalysis of drugs in rat blood: implication for pharmacokinetic studies of anticancer drugs. Springerplus5(1), 1–8 (2016).
  • Skov K , HadrupN, SmedsgaardJ, FrandsenH. LC–MS analysis of the plasma metabolome—A novel sample preparation strategy. J. Chromatogr. B.978, 83–88 (2015).
  • Psychogios N , HauDD, PengJet al. The human serum metabolome. PLoS ONE6(2), e16957 (2011).
  • Josefsson M , SabanovicA. Sample preparation on polymeric solid phase extraction sorbents for liquid chromatographic-tandem mass spectrometric analysis of human whole blood—A study on a number of beta-agonists and beta-antagonists. J. Chromatogr. A1120(1–2), 1–12 (2006).
  • Deda O , GikaHG, WilsonID, TheodoridisGA. An overview of fecal sample preparation for global metabolic profiling. J. Pharm. Biomed. Anal.113, 137–150 (2015).
  • Cao H , HuangH, XuWet al. Fecal metabolome profiling of liver cirrhosis and hepatocellular carcinoma patients by ultra performance liquid chromatography–mass spectrometry. Anal. Chim. Acta691(1–2), 68–75 (2011).
  • Kalariya PD , PatelPN, KavyaPet al. Rapid structural characterization of in vivo and in vitro metabolites of tinoridine using UHPLC–QTOF–MS/MS and in silico toxicological screening of its metabolites. J. Mass Spectrom.50(11), 1222–1233 (2015).
  • Shankar G , BorkarRM, UduthaS, AnagoniSP, SrinivasR. Identification and structural characterization of in vivo metabolites of balofloxacin in rat plasma, urine and feces samples using Q-TOF/LC/ESI/MS/MS: in silico toxicity studies. J. Pharm. Biomed. Anal.159, 200–211 (2018).
  • Linton A , HedgesA, BennettP. Monitoring for the development of antimicrobial resistance during the use of olaquindox as a feed additive on commercial pig farms. J. Appl. Bacteriol.64(4), 311–327 (1988).
  • Bi Y , WangX, XuSet al. Metabolism of olaquindox in rat and identification of metabolites in urine and feces using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom.25(7), 889–898 (2011).
  • Chavan BB , KalariyaPD, NimbalkarRD, GargP, SrinivasR, KumarTalluri M. Identification and characterization of fluvastatin metabolites in rats by UHPLC/Q-TOF/MS/MS and in silico toxicological screening of the metabolites. J. Mass Spectrom.52(5), 296–314 (2017).
  • Wohlfarth A , ScheidweilerKB, ChenX, LiuH-F, HuestisMA. Qualitative confirmation of 9 synthetic cannabinoids and 20 metabolites in human urine using LC–MS/MS and library search. Anal. Chem.85(7), 3730–3738 (2013).
  • Wissenbach DK . Development of the first metabolite-based LC-MSn urine drug screening procedure. 400(1), 79–88 (2012).
  • Zhou G , ShiS, ZhangWet al. Identification of ilaprazole metabolites in human urine by HPLC-ESI-MS/MS and HPLC-NMR experiments. Biomed. Chromatogr.24(10), 1130–1135 (2010).
  • Csajka C , MarzoliniC, FattingerKet al. Population pharmacokinetics and effects of efavirenz in patients with human immunodeficiency virus infection. Clin. Pharmacol. Ther.73(1), 20–30 (2003).
  • Aouri M , BarceloC, TernonBet al. In vivo profiling and distribution of known and novel phase I and phase II metabolites of efavirenz in plasma, urine, and cerebrospinal fluid. Drug Metab. Dispos.44(1), 151–161 (2016).
  • Lu J , HeG, WangXet al. Mass spectrometric identification and characterization of new clomiphene metabolites in human urine by liquid chromatography–quadrupole time-of-flight tandem mass spectrometry. J. Chromatogr. A1243, 23–32 (2012).
  • Morita S , OtsuboK, UchidaM, KawabataS, TamaokaH, ShimizuT. Synthesis and antibacterial activity of the metabolites of 9-fluoro-6, 7-dihydro-8-(4-hydroxy-1-piperidyl)-5-methyl-1-oxo-1H, 5H-benzo [i, j] quinolizine-2-carboxylic acid (OPC-7251). Chem. Pharm. Bull. (Tokyo)38(7), 2027–2029 (1990).
  • Thevis M , PiperT, ThomasA. Recent advances in identifying and utilizing metabolites of selected doping agents in human sports drug testing. J. Pharm. Biomed. Anal.205, 114312 (2021).
  • De Jager AD , WarnerJV, HenmanM, FergusonW, HallA. LC–MS/MS method for the quantitation of metabolites of eight commonly-used synthetic cannabinoids in human urine – an Australian perspective. J. Chromatogr. B.897, 22–31 (2012).
  • Basomba A , PelaezA, VillalmanzoI, CamposA. Allergy to penicillin unsuccessfully treated with a haptenic inhibitor (benzyl-penicilloyl-N2-formil-lysine; BPO-Flys): a case report. Clin. Exp. Allergy8(4), 341–345 (1978).
  • Ho HP , LeeRJ, ChenCY, WangSR, LiZG, LeeMR. Identification of new minor metabolites of penicillin G in human serum by multiple-stage tandem mass spectrometry. Rapid Commun. Mass Spectrom.25(1), 25–32 (2011).
  • Frampton JE . Febuxostat: a review of its use in the treatment of hyperuricaemia in patients with gout. Drugs75(4), 427–438 (2015).
  • Schumacher H Jr , BeckerM, LloydE, MacdonaldP, LademacherC. Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study. Rheumatology (Oxford)48(2), 188–194 (2009).
  • Edwards NL . Febuxostat: a new treatment for hyperuricaemia in gout. Rheumatology (Oxford)48(Suppl. 2), ii15–ii19 (2009).
  • Vincenti M , SalomoneA, GeraceE, PirroV. Application of mass spectrometry to hair analysis for forensic toxicological investigations. Mass Spectrom. Rev.32(4), 312–332 (2013).
  • Pragst F , BalikovaMA. State of the art in hair analysis for detection of drug and alcohol abuse. Clin. Chim. Acta370(1–2), 17–49 (2006).
  • Koster RA , AlffenaarJ-WC, GreijdanusB, VandernagelJE, UgesDR. Fast and highly selective LC-MS/MS screening for THC and 16 other abused drugs and metabolites in human hair to monitor patients for drug abuse. Ther. Drug Monit.36(2), 234–243 (2014).
  • Musshoff F , MadeaB. Analytical pitfalls in hair testing. Anal. Bioanal. Chem.388(7), 1475–1494 (2007).
  • Cappelle D , YeglesM, NeelsHet al. Nail analysis for the detection of drugs of abuse and pharmaceuticals: a review. Forensic Toxicol.33(1), 12–36 (2015).
  • Cappelle D , DeDoncker M, GysCet al. A straightforward, validated liquid chromatography coupled to tandem mass spectrometry method for the simultaneous detection of nine drugs of abuse and their metabolites in hair and nails. Anal. Chim. Acta960, 101–109 (2017).
  • Magalhães TP , CravoS, SilvaDDDet al. Quantification of methadone and main metabolites in nails. J. Anal. Toxicol.42(3), 192–206 (2018).
  • Cobo-Golpe M , De-Castro-RíosA, CruzA, López-RivadullaM, LendoiroE. Determination and distribution of cannabinoids in nail and hair samples. J. Anal. Toxicol. (2020).
  • Ginsburg BC , SchulzeDR, HrubaL, McmahonLR. JWH-018 and JWH-073: Δ9-tetrahydrocannabinol-like discriminative stimulus effects in monkeys. J. Pharmacol. Exp. Ther.340(1), 37–45 (2012).
  • Chung H , ChoiH, HeoS, KimE, LeeJ. Synthetic cannabinoids abused in South Korea: drug identifications by the National Forensic Service from 2009 to June 2013. Forensic Toxicol.32(1), 82–88 (2014).
  • Kim J , InS, ParkY, ParkM, KimE, LeeS. Deposition of JWH-018, JWH-073 and their metabolites in hair and effect of hair pigmentation. Anal. Bioanal. Chem.405(30), 9769–9778 (2013).
  • Park M , YeonS, LeeJ, InS. Determination of XLR-11 and its metabolites in hair by liquid chromatography–tandem mass spectrometry. J. Pharm. Biomed. Anal.114, 184–189 (2015).

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