Response Normalized Liquid Chromatography Nanospray Ionization Mass Spectrometry

Overview

Journal J Am Soc Mass Spectrom

Specialty Chemistry

Date 2007 Sep 4

PMID 17766144

Citations 5

Authors

Ragu Ramanathan

Ruyun Zhong

Neil Blumenkrantz

Swapan K Chowdhury

Kevin B Alton

Affiliations

Soon will be listed here.

Abstract

The widely different LC-MS response observed for many structurally different compounds limits the use of LC-MS in full scan detection mode for quantitative determination of drugs and metabolites without using reference standard. The recently introduced nanospray ionization (NSI) technique shows comparable MS response for some compounds under non-LC-MS conditions. However, in the presence of numerous endogenous compounds commonly associated with biological samples such as urine, plasma, and bile, LC-MS is required to separate, detect, identify, and measure individual analytes. An LC-NSI-MS system was devised and the MS response obtained in this system for a variety of pharmaceutical drugs and their metabolites. The set-up involves two high-performance liquid chromatography (HPLC) systems, a chip-based NSI source and a quadrupole-time-of-flight (Q-TOF) mass spectrometer. Herein this is referred to as the response normalized-liquid chromatography NSI-MS (RNLC-NSI-MS) system. One HPLC unit performs the analytical separation, while the other unit adds solvent post-column with an exact reverse of the mobile phase composition such that the final composition entering the NSI source is isocratic throughout the entire HPLC run. The data obtained from four different structural classes of compounds [vicriviroc (VCV), desloratadine (DL), tolbutamide, and cocaine] and their metabolites indicate that by maintaining the solvent composition unchanged across the HPLC run, the influence of the solvent environment on the ionization efficiency is minimized. In comparison to responses obtained from radiochromatograms, responses from conventional LC-ESI-MS overestimated the VCV and DL responses, respectively, by 6- and 20-fold. Although VCV and DL responses obtained using LC-NSI-MS are within 2- to 6-fold from the respective radiochromatographic responses, the response normalization modification results in nearly uniform LC-NSI-MS response for all compounds evaluated.

Citing Articles

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References

Onorato J, Henion J, Lefebvre P, Kiplinger J . Selected reaction monitoring LC-MS determination of idoxifene and its pyrrolidinone metabolite in human plasma using robotic high-throughput, sequential sample injection. Anal Chem. 2001; 73(1):119-25. DOI: 10.1021/ac000845t. View

Wickremsinhe E, Ackermann B, Chaudhary A . Validating regulatory-compliant wide dynamic range bioanalytical assays using chip-based nanoelectrospray tandem mass spectrometry. Rapid Commun Mass Spectrom. 2004; 19(1):47-56. DOI: 10.1002/rcm.1747. View

Schmidt A, Karas M, Dulcks T . Effect of different solution flow rates on analyte ion signals in nano-ESI MS, or: when does ESI turn into nano-ESI?. J Am Soc Mass Spectrom. 2003; 14(5):492-500. DOI: 10.1016/S1044-0305(03)00128-4. View

Schultz , Corso , Prosser , Zhang . A fully integrated monolithic microchip electrospray device for mass spectrometry. Anal Chem. 2000; 72(17):4058-63. DOI: 10.1021/ac000325y. View

Wickremsinhe E, Singh G, Ackermann B, Gillespie T, Chaudhary A . A review of nanoelectrospray ionization applications for drug metabolism and pharmacokinetics. Curr Drug Metab. 2006; 7(8):913-28. DOI: 10.2174/138920006779010610. View

Wilm M, Mann M . Analytical properties of the nanoelectrospray ion source. Anal Chem. 1996; 68(1):1-8. DOI: 10.1021/ac9509519. View

Zamfir A, Vakhrushev S, Sterling A, Niebel H, Allen M, Peter-Katalinic J . Fully automated chip-based mass spectrometry for complex carbohydrate system analysis. Anal Chem. 2004; 76(7):2046-54. DOI: 10.1021/ac035320q. View

Jemal M . High-throughput quantitative bioanalysis by LC/MS/MS. Biomed Chromatogr. 2000; 14(6):422-9. DOI: 10.1002/1099-0801(200010)14:6<422::AID-BMC25>3.0.CO;2-I. View

Vengurlekar S, Heitkamp J, McCush F, Velagaleti P, Brisson J, Bramer S . A sensitive LC-MS/MS assay for the determination of dextromethorphan and metabolites in human urine--application for drug interaction studies assessing potential CYP3A and CYP2D6 inhibition. J Pharm Biomed Anal. 2002; 30(1):113-24. DOI: 10.1016/s0731-7085(02)00134-6. View

10.

Gorecki T, Lynen F, Szucs R, Sandra P . Universal response in liquid chromatography using charged aerosol detection. Anal Chem. 2006; 78(9):3186-92. DOI: 10.1021/ac060078j. View

11.

Figeys D, Ning Y, Aebersold R . A microfabricated device for rapid protein identification by microelectrospray ion trap mass spectrometry. Anal Chem. 1997; 69(16):3153-60. DOI: 10.1021/ac970057c. View

12.

Froesch M, Bindila L, Baykut G, Allen M, Peter-Katalinic J, Zamfir A . Coupling of fully automated chip electrospray to Fourier transform ion cyclotron resonance mass spectrometry for high-performance glycoscreening and sequencing. Rapid Commun Mass Spectrom. 2004; 18(24):3084-92. DOI: 10.1002/rcm.1733. View

13.

Dethy J, Ackermann B, Delatour C, Henion J, Schultz G . Demonstration of direct bioanalysis of drugs in plasma using nanoelectrospray infusion from a silicon chip coupled with tandem mass spectrometry. Anal Chem. 2003; 75(4):805-11. DOI: 10.1021/ac0260692. View

14.

Corkery L, Pang H, Schneider B, Covey T, Siu K . Automated nanospray using chip-based emitters for the quantitative analysis of pharmaceutical compounds. J Am Soc Mass Spectrom. 2005; 16(3):363-9. DOI: 10.1016/j.jasms.2004.11.018. View

15.

Figeys D, Aebersold R . Nanoflow solvent gradient delivery from a microfabricated device for protein identifications by electrospray ionization mass spectrometry. Anal Chem. 1998; 70(18):3721-7. DOI: 10.1021/ac980502j. View

16.

Balimane P, Pace E, Chong S, Zhu M, Jemal M, Van Pelt C . A novel high-throughput automated chip-based nanoelectrospray tandem mass spectrometric method for PAMPA sample analysis. J Pharm Biomed Anal. 2005; 39(1-2):8-16. DOI: 10.1016/j.jpba.2005.03.043. View

17.

Alfazema L, Richards D, Gelebart S, Mitchell J, Snowden M . Rapid, accurate and precise quantitative drug analysis: comparing liquid chromatography tandem mass spectrometry and chip-based nanoelectrospray ionisation mass spectrometry. Eur J Mass Spectrom (Chichester). 2005; 11(4):393-402. DOI: 10.1255/ejms.772. View

18.

Zhang S, Van Pelt C, Wilson D . Quantitative determination of noncovalent binding interactions using automated nanoelectrospray mass spectrometry. Anal Chem. 2003; 75(13):3010-8. DOI: 10.1021/ac034089d. View

19.

Zhang S, Van Pelt C, Henion J . Automated chip-based nanoelectrospray-mass spectrometry for rapid identification of proteins separated by two-dimensional gel electrophoresis. Electrophoresis. 2003; 24(21):3620-32. DOI: 10.1002/elps.200305585. View

20.

Van Pelt C, Zhang S, Fung E, Chu I, Liu T, Li C . A fully automated nanoelectrospray tandem mass spectrometric method for analysis of Caco-2 samples. Rapid Commun Mass Spectrom. 2003; 17(14):1573-8. DOI: 10.1002/rcm.1087. View