Development of an Ultra Fast Online-solid Phase Extraction (SPE) Liquid Chromatography Electrospray Tandem Mass Spectrometry (LC-ESI-MS/MS) Based Approach for the Determination of Drugs in Pharmacokinetic Studies

Overview

Journal Anal Methods

Specialties Biochemistry
Chemistry

Date 2011 Jun 11

PMID 21660124

Citations 8

Authors

Nils Helge Schebb

Bora Inceoglu

Tristan Rose

Karen Wagner

Bruce D Hammock

Affiliations

Soon will be listed here.

Abstract

High-throughput analyses of a large number of samples for pharmacokinetic (PK) studies are essential in drug development. Analysis of drug candidates from blood using LC-ESI-MS generally requires separation of the plasma fraction followed by various offline sample preparation procedures. This step is a bottleneck that impedes throughput. In order to overcome this difficulty and accelerate analysis in PK and other studies, we developed an approach allowing the direct analysis of low volumes of whole blood (10 μL) after dilution and centrifugation. Samples were injected in an online-SPE-LC-ESI-MS/MS setup allowing a total run time of only 126 s for a full gradient separation. Analytes were extracted from the matrix within 30 s by turbulent flow chromatography. Subsequently, a full gradient separation was carried out within 1.5 minutes on a 50 × 2.1 mm (1.7 μm) RP-18 column and the analytes were sensitively detected by ESI-MS/MS in SRM mode. The performance of this new ultra fast online SPE-LC-ESI-MS/MS approach was demonstrated by the analysis of diclofenac (DCF), a widely used anti-inflammatory drug. DCF eluted at stable retention times (±0.33%) with narrow peak width (FWHM 3.3 ± 0.15 s). The method displays excellent analytical performance, with a limit of detection of 6 fmol on column, a linear range of over four orders of magnitude and a negligible carry over of 0.12 ± 0.03% for DCF. The PK profile of DCF administered by topical and intraperitoneal routes in rats and by oral route in one human volunteer is investigated using this method. Finally, general applicability of the approach for drugs is demonstrated by analysis of rofecoxib and several inhibitors of the soluble epoxide hydrolase. This new method requires only readily available, off the shelf standard LC instrumentation, and is compliant with the requirements of green analytical chemistry.

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References

Barnett J, Chow J, Ives D, Chiou M, Mackenzie R, Osen E . Purification, characterization and selective inhibition of human prostaglandin G/H synthase 1 and 2 expressed in the baculovirus system. Biochim Biophys Acta. 1994; 1209(1):130-9. DOI: 10.1016/0167-4838(94)90148-1. View

Du L, White R . Reducing glycerophosphocholine lipid matrix interference effects in biological fluid assays by using high-turbulence liquid chromatography. Rapid Commun Mass Spectrom. 2008; 22(21):3362-70. DOI: 10.1002/rcm.3747. View

Schmelzer K, Inceoglu B, Kubala L, Kim I, Jinks S, Eiserich J . Enhancement of antinociception by coadministration of nonsteroidal anti-inflammatory drugs and soluble epoxide hydrolase inhibitors. Proc Natl Acad Sci U S A. 2006; 103(37):13646-51. PMC: 1564210. DOI: 10.1073/pnas.0605908103. View

Bones J, Thomas K, Nesterenko P, Paull B . On-line preconcentration of pharmaceutical residues from large volume water samples using short reversed-phase monolithic cartridges coupled to LC-UV-ESI-MS. Talanta. 2008; 70(5):1117-28. DOI: 10.1016/j.talanta.2006.02.026. View

Xin G, Zhou J, Qi L, Li C, Liu P, Li H . Turbulent-flow chromatography coupled on-line to fast high-performance liquid chromatography and mass spectrometry for simultaneous determination of verticine, verticinone and isoverticine in rat plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2010; 878(3-4):435-41. DOI: 10.1016/j.jchromb.2009.12.027. View

Rowland M, Emmons G . Use of dried blood spots in drug development: pharmacokinetic considerations. AAPS J. 2010; 12(3):290-3. PMC: 2895450. DOI: 10.1208/s12248-010-9188-y. View

Verdirame M, Veneziano M, Alfieri A, Di Marco A, Monteagudo E, Bonelli F . Turbulent flow chromatography TFC-tandem mass spectrometry supporting in vitro/vivo studies of NCEs in high throughput fashion. J Pharm Biomed Anal. 2009; 51(4):834-41. DOI: 10.1016/j.jpba.2009.10.005. View

Vinci F, Fabbrocino S, Fiori M, Serpe L, Gallo P . Determination of fourteen non-steroidal anti-inflammatory drugs in animal serum and plasma by liquid chromatography/mass spectrometry. Rapid Commun Mass Spectrom. 2006; 20(22):3412-20. DOI: 10.1002/rcm.2748. View

Smalley J, Marino A, Xin B, Olah T, Balimane P . Development of a quantitative LC-MS/MS analytical method coupled with turbulent flow chromatography for digoxin for the in vitro P-gp inhibition assay. J Chromatogr B Analyt Technol Biomed Life Sci. 2007; 854(1-2):260-7. DOI: 10.1016/j.jchromb.2007.04.030. View

10.

Niederlander H, Koster E, Hilhorst M, Metting H, Eilders M, Ooms B . High throughput therapeutic drug monitoring of clozapine and metabolites in serum by on-line coupling of solid phase extraction with liquid chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2006; 834(1-2):98-107. DOI: 10.1016/j.jchromb.2006.02.042. View

11.

Imig J, Hammock B . Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. Nat Rev Drug Discov. 2009; 8(10):794-805. PMC: 3021468. DOI: 10.1038/nrd2875. View

12.

Inceoglu B, Jinks S, Schmelzer K, Waite T, Kim I, Hammock B . Inhibition of soluble epoxide hydrolase reduces LPS-induced thermal hyperalgesia and mechanical allodynia in a rat model of inflammatory pain. Life Sci. 2006; 79(24):2311-9. PMC: 1904345. DOI: 10.1016/j.lfs.2006.07.031. View

13.

Gebhardt W, Schroder H . Liquid chromatography-(tandem) mass spectrometry for the follow-up of the elimination of persistent pharmaceuticals during wastewater treatment applying biological wastewater treatment and advanced oxidation. J Chromatogr A. 2007; 1160(1-2):34-43. DOI: 10.1016/j.chroma.2007.05.075. View

14.

Suenami K, Lim L, Takeuchi T, Sasajima Y, Sato K, Takekoshi Y . On-line sample extraction and enrichment of non-steroidal anti-inflammatory drugs by pre-column in capillary liquid chromatography mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2006; 846(1-2):176-83. DOI: 10.1016/j.jchromb.2006.08.041. View

15.

Xu Y, Willson K, Anderson M, Musson D, Miller-Stein C, Woolf E . Elimination of diastereomer interference to determine Telcagepant (MK-0974) in human plasma using on-line turbulent-flow technology and off-line solid-phase extraction coupled with liquid chromatography/tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2009; 877(16-17):1634-42. DOI: 10.1016/j.jchromb.2009.04.006. View

16.

Mottier P, Hammel Y, Gremaud E, Guy P . Quantitative high-throughput analysis of 16 (fluoro)quinolones in honey using automated extraction by turbulent flow chromatography coupled to liquid chromatography-tandem mass spectrometry. J Agric Food Chem. 2007; 56(1):35-43. DOI: 10.1021/jf072934d. View

17.

Siemerink M, Schebb N, Liesener A, Perchuc A, Schoni R, Wilmer M . Development of a fast liquid chromatography/mass spectrometry screening method for angiotensin-converting enzyme (ACE) inhibitors in complex natural mixtures like snake venom. Rapid Commun Mass Spectrom. 2010; 24(5):687-97. DOI: 10.1002/rcm.4428. View

18.

Xu R, Fan L, Rieser M, El-Shourbagy T . Recent advances in high-throughput quantitative bioanalysis by LC-MS/MS. J Pharm Biomed Anal. 2007; 44(2):342-55. DOI: 10.1016/j.jpba.2007.02.006. View

19.

Li W, Tse F . Dried blood spot sampling in combination with LC-MS/MS for quantitative analysis of small molecules. Biomed Chromatogr. 2009; 24(1):49-65. DOI: 10.1002/bmc.1367. View

20.

Zhou S, Zhou H, Larson M, Miller D, Mao D, Jiang X . High-throughput biological sample analysis using on-line turbulent flow extraction combined with monolithic column liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2005; 19(15):2144-50. DOI: 10.1002/rcm.2037. View