Liquid Chromatography Drug screening

Olah, T. V., McLoughlin, D. A., Gilbert, J. D., The simultaneous determination of mixtures of drug candidates by liquid chromatography/ atmospheric pressure chemical ionisation mass spectrometry as an in-vivo drug screening procedure, Rapid Commun. Mass Spec. 1997, 11, 17—23. 

Beaudry F. et al., 1998. In vivo pharmacokinetic screening in cassette dosing experiments Use of online Pros-pekt liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry technology in drug discovery. Rapid Commun Mass Spectrom 12 1216. 

Hsieh Y. et al., 2001. Quantitative screening and matrix effect studies of drug discovery compounds in monkey plasma using fast-gradient liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 15 2481. 

Gergov M, Ojanpera I, Vuori E. 2003. Simultaneous screening for 238 drugs in blood by liquid chromatography-ionspray tandem mass spectrometry with multiple-reaction monitoring. J Chromatogr B 795 41. 

Hopfgartner, G. The combination of liquid chromatography/tandem mass spectrometry and chip-based infusion for improved screening and characterization of drug metabolites. Rapid Commun. Mass Spectrom. 2005, 19, 618-626. 

K. J. Veals, J. Hsieh, Y. etal. Cassette-accelerated rapid rat screen a systematic procedure for the dosing and liquid chromatography/ atmospheric pressure ionization tandem mass spectrometric analysis of new chemical entities as part of new drug discovery. Rapid Commun Mass Spectrom 2001, 15, 335-340. 

Ho, E.N.M., Leung, D.K.K., Wan, T.S.M. and Yu, N.H. (2006) Comprehensive Screening of Anabolic Steroids, Corticosteroids, and Acidic Drugs in Horse Urine by Solid-Phase Extraction and Liquid Chromatography-Mass Spectrometry. J Chromatopfr A, 1120, 38. 

Modern drug discovery approaches involve HTS, where, applying full automation and robotics, hundreds of molecules can be screened using several assays within a short time, and with very little amounts of compounds. In order to incorporate natural products in the modern HTS programmes, a natural product library (a collection of dereplicated natural products) needs to be built. Dereplication is the process by which one can eliminate recurrence or re-isolation of same or similar compounds from various extracts. A number of hyphenated techniques are used for dereplication, e.g. LC-PDA (liquid chromatography-photo-diode-array detector). 

Femandez-Metzler, C. L., Owens, K. G., Baillie, T. A., and King, R. C. (1999). Rapid liquid chromatography with tandem mass spectrometry-based screening procedures for studies on the biotransformation of drug candidates. Drug Metab. Dispos. 27 32-40. 

Hsieh, Y., Chintala, M., Mei, H., Agans, J., Brisson, J. M., Ng, K., and Korfmacher, W. A. (2001). Quantitative screening and matrix effect studies of drug discovery compounds in monkey plasma [by] using fast-gradient liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass Spectrom. 15 2481-2487. 

Mortishire-Smith, R. J., O Connor, D., Castro-Perez, J. M., and Kirby, J. (2005). 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 2659-2670. 

C. C. 1997. Pharmacokinetic screening for the selection of new drug discovery candidates is greatly enhanced through the use of liquid chromatography-atmospheric pressure ionization tandem mass spectrometry. J. Chromatogr. A, 777,61-66. 

Synthetic peptides often lack the conformational stability required for a successful drug therefore determination of peptide stability in serum constitutes a powerful and important screening assay for the elimination of unstable peptides in the pipeline of drug development (see Note 1). Peptide stability in serum can rather easily be determined by reverse phase-high-performance liquid chromatography (RP-HPLC) and mass spectroscopy (MS) from both in vitro and in vivo studies. 

Allen KR (2006) Interference by venlafaxine ingestion in the detection of tramadol by liquid chromatography linked to tandem mass spectrometry for the screening of illicit drugs in human urine. Clin Toxicol 44 147-153... 

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