404
Views
4
CrossRef citations to date
0
Altmetric
Review

Integration of Microfluidic LC with HRMS for The Analysis of Analytes in Biofluids: Past, Present and Future

, , , &
Pages 1397-1411 | Published online: 25 Jun 2015

References

  • Plumb RS , RainvillePD, PottsWB, JohnsonKA, GikaE, WilsonID. Application of ultra performance liquid chromatography−mass spectrometry to profiling rat and dog bile. J. Proteome Res. 8 (5), 2495–2500 (2009).
  • Plumb RS , PottsWB, RainvillePDet al. Addressing the analytical throughput challenges in ADME screening using rapid ultra-performance liquid chromatography/tandem mass spectrometry methodologies. Rapid Commun. Mass Spectrom. 22 (14), 2139–2152 (2008).
  • Berna M , OttL, EngleS, WatsonD, SolterP, AckermannB. Quantification of NTproBNP in rat serum using immunoprecipitation and LC–MS/MS: a biomarker of drug-induced cardiac hypertrophy. Anal. Chem. 80 (3), 561–566 (2008).
  • Horvath TD , StrattonSL, BogusiewiczA, PackL, MoranJ, MockDM. Quantitative measurement of plasma 3-hydroxyisovaleryl carnitine by LC-MS/MS as a novel biomarker of biotin status in humans. Anal. Chem. 82 (10), 4140–4144 (2010).
  • Zhang Q , SpellmanDS, SongYet al. Generic automated method for liquid chromatography–multiple reaction monitoring mass spectrometry based monoclonal antibody quantitation for preclinical pharmacokinetic studies. Anal. Chem. 86 (17), 8776–8784 (2014).
  • Clarke NJ , RindgenD, KorfmacherWA, CoxKA. Peer reviewed: systematic LC–MS metabolite identification in drug discovery. Anal. Chem. 73 (15), 430A–439A (2001).
  • Hsu J-F , PengL-W, LiY-J, LinL-C, LiaoP-C. Identification of di-isononyl phthalate metabolites for exposure marker discovery using in vitro/in vivo metabolism and signal mining strategy with LC-MS data. Anal. Chem. 83 (22), 8725–8731 (2011).
  • Zhang N , FountainST, BiH, RossiDT. Quantification and rapid metabolite identification in drug discovery using API time-of-flight LC–MS. Anal. Chem. 72 (4), 800–806 (2000).
  • Theodoridis G , GikaHG, WilsonID. LC–MS-based methodology for global metabolite profiling in metabonomics/metabolomics. TrAC-Trend. Anal. Chem. 27 (3), 251–260 (2008).
  • Crockford DJ , HolmesE, LindonJCet al. Statistical heterospectroscopy, an approach to the integrated analysis of NMR and UPLC-MS data sets: application in metabonomic toxicology studies. Anal. Chem. 78 (2), 363–371 (2005).
  • Dunn WB , EllisDI. Metabolomics: current analytical platforms and methodologies. TrAC-Trend. Anal. Chem. 24 (4), 285–294 (2005).
  • Kind T , TolstikovV, FiehnO, WeissRH. A comprehensive urinary metabolomic approach for identifying kidney cancer. Anal. Biochem. 363 (2), 185–195 (2007).
  • Liland KH . Multivariate methods in metabolomics – from pre-processing to dimension reduction and statistical analysis. TrAC-Trend. Anal. Chem. 30 (6), 827–841 (2011).
  • Lindon JC , NicholsonJK. Spectroscopic and statistical techniques for information recovery in metabonomics and metabolomics. Annu. Rev. Anal. Chem. 1 (1), 45–69 (2008).
  • Scott RPW , ScottCG, MunroeM, HessJrJ. Interface for on-line liquid chromatography–mass spectroscopy analysis. J. Chromatogr. A99 (0), 395–405 (1974).
  • Games DE , McdowallMA, LevsenK, SchaferKH, DobbersteinP, GowerJL. A comparison of moving belt interfaces for liquid chromatography mass spectrometry. Biol. Mass Spectrom. 11 (2), 87–95 (1984).
  • Hayes MJ , LankmayerEP, VourosP, KargerBL, McguireJM. Moving belt interface with spray deposition for liquid chromatography/mass spectrometry. Anal. Chem. 55 (11), 1745–1752 (1983).
  • Whitehouse CM , DreyerRN, YamashitaM, FennJB. Electrospray interface for liquid chromatographs and mass spectrometers. Anal. Chem. 57 (3), 675–679 (1985).
  • Covey TR , CrowtherJB, DeweyEA, HenionJD. Thermospray liquid chromatography/mass spectrometry determination of drugs and their metabolites in biological fluids. Anal. Chem. 57 (2), 474–481 (1985).
  • Ishii D , AsaiK, HibiK, JonokuchiT, NagayaM. A study of micro-high-performance liquid chromatography: I. Development of technique for miniaturization of high-performance liquid chromatography. J. Chromatogr. A144 (2), 157–168 (1977).
  • Novotny M . Capillary HPLC. Columns and related instrumentation. J. Chromatogr. Sci. 18 (9), 473–478 (1980).
  • Vissers JPC , BlackburnRK, MoseleyMA. A novel interface for variable flow nanoscale LC–MS/MS for improved proteome coverage. J. Am. Soc. Mass Spectrom. 13 (7), 760–771 (2002).
  • Peng J , EliasJE, ThoreenCC, LickliderLJ, GygiSP. Evaluation of multidimensional chromatography coupled with tandem mass spectrometry (LC/LC−MS/MS) for Large-scale protein analysis: the yeast proteome. J. Proteome Res. 2 (1), 43–50 (2002).
  • Livesay EA , TangK, TaylorBKet al. Fully automated four-column capillary LC−MS system for maximizing throughput in proteomic analyses. Anal. Chem. 80 (1), 294–302 (2007).
  • Lu B , MotoyamaA, RuseC, VenableJ, YatesJR. Improving protein identification sensitivity by combining MS and MS/MS information for shotgun proteomics using LTQ-Orbitrap high mass accuracy data. Anal. Chem. 80 (6), 2018–2025 (2008).
  • Rappsilber J , IshihamaY, MannM. Stop and go extraction tips for matrix-assisted laser desorption/ionization, nanoelectrospray, and LC–MS sample pretreatment in proteomics. Anal. Chem. 75 (3), 663–670 (2002).
  • Davis MT , StahlDC, HeftaSA, LeeTD. A microscale electrospray interface for online, capillary liquid chromatography/tandem mass spectrometry of complex peptide mixtures. Anal. Chem. 67 (24), 4549–4556 (1995).
  • Choudhary G , WuS-L, ShiehP, HancockWS. Multiple enzymatic digestion for enhanced sequence coverage of proteins in complex proteomic mixtures using capillary LC with Ion trap MS/MS. J. Proteome Res. 2 (1), 59–67 (2002).
  • Davis M , LeeT. Rapid protein identification using a microscale electrospray LC–MS system on an ion trap mass spectrometer. J. Am. Soc. Mass. Spectrom. 9 (3), 194–201 (1998).
  • Wilm M , MannM. Analytical properties of the nanoelectrospray ion source. Anal. Chem. 68 (1), 1–8 (1996).
  • Delahunty C , Yates IiiJR. Protein identification using 2D-LC-MS/MS. Methods35 (3), 248–255 (2005).
  • Vissers JPC , ClaessensHA, CramersCA. Microcolumn liquid chromatography: instrumentation, detection and applications. J. Chromatogr. A779 (1–2), 1–28 (1997).
  • Mather J , RainvillePD, Potts IiiWB, SmithNW, PlumbRS. Development of a high sensitivity bioanalytical method for alprazolam using ultra-perfor-mance liquid chromatography/tandem mass spectrometry. Drug Test. Anal. 2 (1), 11–18 (2010).
  • Pedraglio S , RozioMG, MisianoP, RealiV, DondioG, BigognoC. New perspectives in bio-analytical techniques for preclinical characterization of a drug candidate: UPLC-MS/MS in in vitro metabolism and pharmacokinetic studies. J. Pharm. Biomed. Anal. 44 (3), 665–673 (2007).
  • Brewer E , HenionJ. Atmospheric pressure ionization LC–MS/MS techniques for drug disposition studies. J. Pharm. Sciences87 (4), 395–402 (1998).
  • Lee MS , KernsEH. LC–MS applications in drug development. Mass Spectrom. Rev. 18 (3–4), 187–279 (1999).
  • Mazzeo JR , NeueDU, KeleM, PlumbRS. Advancing LC Performance with Smaller Particles and Higher Pressure. Anal. Chem. 77 (23), 460A–467A (2005).
  • Xu RN , FanL, RieserMJ, El-ShourbagyTA. Recent advances in high-throughput quantitative bioanalysis by LC–MS/MS. J. Pharm. Biomed. Anal. 44 (2), 342–355 (2007).
  • Plumb RS , DearGJ, MallettD, FraserIJ, AyrtonJ, IoannouC. The application of fast gradient capillary liquid chromatography/mass spectrometry to the analysis of pharmaceuticals in biofluids. Rapid Commun. Mass Spectrom. 13 (10), 865–872 (1999).
  • Fraser IJ , DearGJ, PlumbR, L’affineurM, FraserD, SkippenAJ. The use of capillary high performance liquid chromatography with electrospray mass spectrometry for the analysis of small volume blood samples from serially bled mice to determine the pharmacokinetics of early discovery compounds. Rapid Commun. Mass Spectrom. 13 (23), 2366–2375 (1999).
  • Plumb RS , WarwickH, HigtonD, DearGJ, MallettDN. Determination of 4-hydroxytamoxifen in mouse plasma in the pg/mL range by gradient capillary liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass Spectrom. 15 (4), 297–303 (2001).
  • Ayrton J , ClareRA, DearGJ, MallettDN, PlumbRS. Ultra-high flow rate capillary liquid chromatography with mass spectrometric detection for the direct analysis of pharmaceuticals in plasma at sub-nanogram per millilitre concentrations. Rapid Commun. Mass Spectrom. 13 (16), 1657–1662 (1999).
  • Dear GJ , AyrtonJ, PlumbR, FraserIJ. The rapid identification of drug metabolites using capillary liquid chromatography coupled to an ion trap mass spectrometer. Rapid Commun. Mass Spectrom. 13 (5), 456–463 (1999).
  • Lenz EM , WilliamsRE, SidawayJet al. The application of microbore UPLC/oa-TOF-MS and 1H NMR spectroscopy to the metabonomic analysis of rat urine following the intravenous administration of pravastatin. J. Pharm. Biomed. Anal. 44 (4), 845–852 (2007).
  • Mortishire-Smith RJ , O’connorD, Castro-PerezJM, KirbyJ. Accelerated throughput metabolic route screening in early drug discovery using high-resolution liquid chromatography/quadrupole time-of-flight mass spectrometry and automated data analysis. Rapid Commun. Mass Spectrom. 19 (18), 2659–2670 (2005).
  • Sanders M , ShipkovaPA, ZhangH, WarrackBM. Utility of the hybrid LTQ-FTMS for drug metabolism applications. Curr. Drug Metab. 7 (5), 547–555 (2006).
  • Ma S , ChowdhurySK. Analytical strategies for assessment of human metabolites in preclinical safety testing. Anal. Chem. 83 (13), 5028–5036 (2011).
  • Josefsson M , RomanM. Rapid and accurate forensics analysis using high resolution all ions MS/MS - agilent application note 5991–2319EN. (2013). www.chem.agilent.com/Library/applications/5991-2319EN.pdf.
  • Roman M , StromL, TellH, JosefssonM. Liquid chromatography/time-of-flight mass spectrometry analysis of postmortem blood samples for targeted toxicological screening. Anal. Bioanal. Chemistry405 (12), 4107–4125 (2013).
  • Andrews GL , SimonsBL, YoungJB, HawkridgeAM, MuddimanDC. Performance characteristics of a new hybrid triple quadrupole time-of-flight tandem mass spectrometer. Anal. Chem. 83 (13), 5442–5446 (2011).
  • Geiger T , CoxJ, MannM. Proteomics on an orbitrap benchtop mass spectrometer using all-ion fragmentation. Mol. Cell. Proteomics9 (10), 2252–2261 (2010).
  • Silva JC , DennyR, DorschelCAet al. Quantitative proteomic analysis by accurate mass retention time pairs. Anal. Chem. 77 (7), 2187–2200 (2005).
  • Zhang H , HenionJ. Comparison between liquid chromatography–time-of-flight mass spectrometry and selected reaction monitoring liquid chromatography–mass spectrometry for quantitative determination of idoxifene in human plasma. J. Chromatogr. B (757), 151–159 (2001).
  • Zhang N , FountainS, BiH, RossiDT. Quantification and rapid metabolite identification in drug discovery using api time-of-flight LC–MS. Anal. Chem. 72, 800–806 (2000).
  • Van Dongen WD , NiessenWMA. LC-MS systems for quantitative bioanalysis. Bioanalysis4 (19), 2391–2399 (2012).
  • Ramanathan R , JemalM, RamagiriSet al. It is time for a paradigm shift in drug discovery bioanalysis: from SRM to HRMS. J. Mass Spectrom. 46 (6), 595–601 (2011).
  • Hamelin EI , BraggW, ShanerRL, SwaimLL, JohnsonRC. Comparison of high-resolution and tandem mass spectrometry for the analysis of nerve agent metabolites in urine. Rapid Commun. Mass Spectrom. 27 (15), 1697–1704 (2013).
  • Henry H , SobhiHR, ScheibnerO, BromirskiM, NimkarSB, RochatB. Comparison between a high-resolution single-stage Orbitrap and a triple quadrupole mass spectrometer for quantitative analyses of drugs. Rapid Commun. Mass Spectrom. 26 (5), 499–509 (2012).
  • Morin L-P , MessJ-N, GarafaloF. Large-molecule quantification: sensitivity and selectivity head-to-head comparison of triple quadrupole with Q-TOF. Bioanalysis5 (10), 1181–1193 (2013).
  • Mess J-N , LandryF, GarofoloF. Quantitative bioanalysis of small and large molecules by high-resolution MS. In : Applications of High-Resolution Mass Spectrometry in Drug Discovery and Development. SlenoL ( Ed.). Future Science Ltd, London, UK, 59–73 (2014).
  • Kaufmann A , WalkerS. Evaluation of the interrelationship between mass resolving power and mass error tolerances for targeted bioanalysis using liquid chromatography coupled to high-resolution mass spectrometry. Rapid Commun. Mass Spectrom. 27 (2), 347–356 (2013).
  • Xia Y-Q , LauJ, OlahT, JemalM. Targeted quantitative bioanalysis in plasma using liquid chromatography/high-resolution accurate mass spectrometry: an evaluation of global selectivity as a function of mass resolving power and extraction window, with comparison of centroid and profile modes. Rapid Commun. Mass Spectrom. 25 (19), 2863–2878 (2011).
  • Jiang J , JamesCA, WongP. Determination of rosiglitazone and 5-hydroxy rosiglitazone in rat plasma using LC–HRMS by direct and indirect quantitative analysis: a new approach for metabolite quantification. Bioanalysis5 (15), 1873–1881 (2013).
  • Huang M-Q , LinZ, WengN. Applications of high-resolution MS in bioanalysis. Bioanalysis5 (10), 1269–1276 (2013).
  • Dillen L , CoolsW, VereykenLet al. Comparison of triple quadrupole and high-resolution TOF-MS for quantification of peptides. Bioanalysis4 (5), 565–579 (2012).
  • Mekhssian K , MessJ-N, GarofoloF. Application of high-resolution MS in the quantification of a therapeutic monoclonal antibody in human plasma. Bioanalysis6 (13), 1767–1779 (2014).
  • Rochat B , PeduzziD, McmullenJet al. Validation of hepcidin quantification in plasma using LC–HRMS and discovery of a new hepcidin isoform. Bioanalysis5 (20), 2509–2520 (2013).
  • Yuan W , EdwardsJL. Capillary separations in metabolomics. Bioanalysis2 (5), 953–963 (2010).
  • Ding J , SorensenCM, ZhangQet al. Capillary LC coupled with high-mass measurement accuracy mass spectrometry for metabolic profiling. Anal. Chem. 79 (16), 6081–6093 (2007).
  • Myint KT , AoshimaK, TanakaS, NakamuraT, OdaY. Quantitative profiling of polar cationic metabolites in human cerebrospinal fluid by reversed-phase nanoliquid chromatography/mass spectrometry. Anal. Chem. 81 (3), 1121–1129 (2009).
  • Myint KT , UeharaT, AoshimaK, OdaY. Polar anionic metabolome analysis by nano-LC–MS with a metal chelating agent. Anal. Chem. 81 (18), 7766–7772 (2009).
  • Uehara T , YokoiA, AoshimaKet al. Quantitative phosphorus metabolomics using nanoflow liquid chromatography-tandem mass spectrometry and culture-derived comprehensive global internal standards. Anal. Chem. 81 (10), 3836–3842 (2009).
  • Plumb RS , GrangerJH, StumpfCLet al. A rapid screening approach to metabonomics using UPLC and oa-TOF mass spectrometry: application to age, gender and diurnal variation in normal/Zucker obese rats and black, white and nude mice. Analyst130 (6), 844–849 (2005).
  • Wilson ID , NicholsonJK, Castro-PerezJet al. High resolution “ultra performance” liquid chromatography coupled to oa-tof mass spectrometry as a tool for differential metabolic pathway profiling in functional genomic studies. J. Proteome Res. 4 (2), 591–598 (2005).
  • Jones DR , WuZ, ChauhanD, AndersonKC, PengJ. A nano ultra-performance liquid chromatography–high resolution mass spectrometry approach for global metabolomic profiling and case study on drug-resistant multiple myeloma. Anal. Chem. 86 (7), 3667–3675 (2014).
  • Gao X , ZhangQ, MengDet al. A reversed-phase capillary ultra-performance liquid chromatography–mass spectrometry (UPLC-MS) method for comprehensive top-down/bottom-up lipid profiling. Anal. Bioanal. Chem. 402 (9), 2923–2933 (2012).
  • Granger J , PlumbR, Castro-PerezJ, WilsonID. Metabonomic studies comparing capillary and conventional HPLC-oa-TOF MS for the analysis of urine from Zucker obese rats. Chroma61 (7–8), 375–380 (2005).
  • Manz A , MiyaharaY, MiuraJ, WatanabeY, MiyagiH, SatoK. Design of an open-tubular column liquid chromatograph using silicon chip technology. Sens. Actuators B-Chem. 1 (1–6), 249–255 (1990).
  • Lazar IM , RamseyRS, SundbergS, RamseyJM. Subattomole-sensitivity microchip nanoelectrospray source with time-of-flight mass spectrometry detection. Anal. Chem. 71 (17), 3627–3631 (1999).
  • Ramsey JD , JacobsonSC, CulbertsonCT, RamseyJM. High-efficiency, two-dimensional separations of protein digests on microfluidic devices. Anal. Chem. 75 (15), 3758–3764 (2003).
  • Ramsey RS , RamseyJM. Generating electrospray from microchip devices using electroosmotic pumping. Anal. Chem. 69 (6), 1174–1178 (1997).
  • Van Pelt CK , ZhangS, FungEet al. A fully automated nanoelectrospray tandem mass spectrometric method for analysis of Caco-2 samples. Rapid Commun. Mass Spectrom. 17 (14), 1573–1578 (2003).
  • Wickremsinhe ER , AckermannBL, ChaudharyAK. Validating regulatory-compliant wide dynamic range bioanalytical assays using chip-based nanoelectrospray tandem mass spectrometry. Rapid Commun. Mass Spectrom. 19 (1), 47–56 (2005).
  • Yin H , KilleenK, BrennenR, SobekD, WerlichM, Van De GoorT. Microfluidic chip for peptide analysis with an integrated HPLC column, sample enrichment column, and nanoelectrospray tip. Anal. Chem. 77 (2), 527–533 (2004).
  • Hop CECA . Use of nano-electrospray for metabolite identification and quantitativeabsorption, distribution, metabolism and excretion studies. Curr. Drug Metab. 7 (5), 7 (2006).
  • Robotti KM , YinH, BrennenR, TrojerL, KilleenK. Microfluidic HPLC-Chip devices with integral channels containing methylstyrenic-based monolithic media. J. Sep. Sci. 32 (20), 3379–3387 (2009).
  • Agilent Technologies . HPLC-Chip Cube MS Interface. www.chem.agilent.com/en-US/products-services/Instruments-Systems/Mass-Spectrometry/hplc-chip-cube-msinterface/Pages/default.aspx.
  • Eksigent cHiPLC system. www.eksigent.com/hplc-products/chip-hplc-systems/chiplc-system.
  • Waters ionKey/MS system. www.waters.com/waters/en_US/ionKey-MS‐‐-the-integration-of-the-UPLC-separation-into-the-source-of-the-mass-spectrometer/nav.htm?cid=134782630.
  • Rainville PD , DoneanuC. Robustness of ionKey/MS System in the Analysis of Pharmaceutical Compounds in Biological Fluids. Waters Application Note, APNT134783313, 1–4 (2014).
  • Broccardo CJ , SchauerKL, KohrtWM, SchwartzRS, MurphyJP, PrenniJE. Multiplexed analysis of steroid hormones in human serum using novel microflow tile technology and LC–MS/MS. J. Chromatogr. B934 (0), 16–21 (2013).
  • Laiakis EC , StrassburgK, BogumilRet al. Metabolic phenotyping reveals a lipid mediator response to ionizing radiation. J. Proteome Res. 13 (9), 4143–4154 (2014).
  • Astarita G MJ , WangBet al. A protective lipidomic biosignature associated with a balanced omega-6/omega-3 ratio. PLoS ONE9 (4), 11 (2014).
  • Chu CS , NiñonuevoMR, ClowersBHet al. Profile of native N-linked glycan structures from human serum using high performance liquid chromatography on a microfluidic chip and time-of-flight mass spectrometry. Proteomics9 (7), 1939–1951 (2009).
  • Bai H-Y , LinS-L, ChungY-T, LiuT-Y, ChanS-A, FuhM-R. Quantitative determination of 8-isoprostaglandin F2α in human urine using microfluidic chip-based nano-liquid chromatography with on-chip sample enrichment and tandem mass spectrometry. J. Chromatogr. A1218 (15), 2085–2090 (2011).
  • Zamfir A , VukelićŽ, BindilaLet al. Fully-automated chip-based nanoelectrospray tandem mass spectrometry of gangliosides from human cerebellum. J. Am. Soc. Mass Spectrom. 15 (11), 1649–1657 (2004).
  • Houbart V , ServaisA-C, CharlierTD, PawluskiJL, AbtsF, FilletM. A validated microfluidics-based LC-chip-MS/MS method for the quantitation of fluoxetine and norfluoxetine in rat serum. Electrophoresis33 (22), 3370–3379 (2012).
  • Bai H-Y , LinS-L, ChanS-A, FuhM-R. Characterization and evaluation of two-dimensional microfluidic chip-HPLC coupled to tandem mass spectrometry for quantitative analysis of 7-aminoflunitrazepam in human urine. Analyst135 (10), 2737–2742 (2010).
  • Min JZ , YanoH, MatsumotoAet al. Simultaneous determination of polyamines in human nail as 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole derivatives by nano-flow chip LC coupled with quadrupole time-of-flight tandem mass spectrometry. Clin. Chim. Acta412 (1–2), 98–106 (2011).
  • Hua S , WilliamsCC, DimapasocLMet al. Isomer-specific chromatographic profiling yields highly sensitive and specific potential N-glycan biomarkers for epithelial ovarian cancer. J. Chromatogr. A1279 (0), 58–67 (2013).
  • Rafalko A , DaiS, HancockWS, KargerBL, HincapieM. Development of a Chip/Chip/SRM platform using digital chip isoelectric focusing and LC-Chip mass spectrometry for enrichment and quantitation of low abundance protein biomarkers in human plasma. J. Proteome Res. 11 (2), 808–817 (2011).
  • Hop CE . Use of nano-electrospray for metabolite identification and quantitative absorption, distribution, metabolism and excretion studies. Curr. Drug Metab. 7 (6), 7 (2006).
  • Kirsch S , BindilaL. Nano-LC and HPLC-chip–ESI–MS: an emerging technique for glycobioanalysis. Bioanalysis1 (7), 1307–1327 (2009).
  • Calipo L , FogliaP, GubbiottiR, SamperiR, LaganàA. HPLC-CHIP coupled to a triple quadrupole mass spectrometer for carbonic anhydrase II quantification in human serum. Anal. Bioanal. Chem. 394 (3), 9 (2009).
  • Lee H , LernoLA, ChoeYet al. Multiple precursor ion scanning of gangliosides and sulfatides with a reversed-phase microfluidic chip and quadrupole time-of-flight mass spectrometry. Anal. Chem. 84 (14), 5905–5912 (2012).
  • Paglia G , AngelP, WilliamsJPet al. Ion mobility-derived collision cross section as an additional measure for lipid fingerprinting and identification. Anal. Chem. 87 (2), 1137–1144 (2014).
  • Rainville PD , SmithNW, WilsonID, NicholsonJK, PlumbRS. Addressing the challenge of limited sample volumes in in vitro studies with capillary-scale microfluidic LC–MS/MS. Bioanalysis3 (8), 873–882 (2011).
  • Gallagher R , DillonL, GrimsleyA, MurphyJ, SamuelssonK, DouceD. The application of a new microfluidic device for the simultaneous identification and quantitation of midazolam metabolites obtained from a single micro-litre of chimeric mice blood. Rapid Commun. Mass Spectrom. 28 (11), 1293–1302 (2014).
  • Rainville PD , TheodoridisG, PlumbRS, WilsonID. Advances in liquid chromatography coupled to mass spectrometry for metabolic phenotyping. TrAC-Trend. Anal. Chem. 61 (0), 181–191 (2014).
  • Hua S , LebrillaC, AnHJ. Application of nano-LC-based glycomics towards biomarker discovery. Bioanalysis3 (22), 2573–2585 (2011).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.