Tandem mass spectrometry Biotransformation

Anari MR, Sanchez RI, Bakhtiar R, Franklin RB, Baillie TA. Integration of knowledge-based metabolic predictions with liquid chromatography data-dependent tandem mass spectrometry for drug metabolism studies application to studies on the biotransformation of indinavir. Anal Chem 2004 76 823-32. 

Jahnke, A., Gandrass, J., Ruck, W. (2004). Simultaneous determination of alkylphenol ethoxylates and their biotransformation products by liquid chromatography/electrospray ionisation tandem mass spectrometry. J. Chromatogr. A 1035(1), 115-122. 

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. 

Superior sensitivity, efficiency, and specificity have made high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), the predominant analytical technique for characterization and quantitative analysis of metabolites (Kostiainen et al., 2003 Ma et al., 2006 Prakash et al., 2007). Ion trap, triple-quadrupole, and quadmpole time-of-flight (Q-TOF) mass spectrometers are routinely used to profile and characterize metabolites in plasma and excreta (Ma et al., 2006). The combination of scan types and features available on mass spectrometers of different design (product ion, MS", neutral loss, precursor ion scans, accurate mass measurements) allows identification and characterization of putative and unexpected metabolites with or without little prior knowledge of biotransformation pathways of a given dmg molecule. 

Jemal, M., Ouyang, Z., Xia, Y. Q., and Powell, M. L. (1999b). A versatile system of high-flow high performance liquid chromatography with tandem mass spectrometry for rapid direct-injection analysis of plasma samples for quantitation of a beta-lactam drug candidate and its open-ring biotransformation product. Rapid Commun. Mass Spectrom. 13 1462-1471. 

J. Mohammed, O. Zheng, C.C. Bang, T. Deborah, Quantitation of the acid and lactone forms of atorvastatin and its biotransformation products in human serum by high-performance liquid chromatography with electrospray tandem mass spectrometry, Rapid Commun. Mass Spectrom. 13 (1999) 1003-1015. 

Fernandez-Metzler, C.L. Owens, K.G. Baillie, T.A. King, R.C. Rapid Liquid Chromatography with Tandem Mass Spectrometry-based Screening Procedures for Studies on the Biotransformation of Drug Candidates, Drug Metab. Dispos. 27, 32-40 (1999). 

Jemal, M. Ouyang, Z. Xia, Y.-Q. Powell, M.L. A Versatile System of High-Flow High Performance Liquid Chromatography with Tandem Mass Spectrometry for Rapid Direct-Injection Analysis of Plasma Samples for Quantitation of a p -Lactam Drug Candidate and its Open Ring Biotransformation Product, Rapid Commun. Mass Spectrom. 13(14), 1462-1471 (1999). 

Jemal, M. Rao, S. Salahudeen, I. Chen, B.-C. Kates, R. Quantitation of cerivastatin and its seven add and lactone biotransformation products in human serum by hquid chromatography-electrospray tandem mass spectrometry, J.Chromatogr.B, 1999, 736, 19-41. 

Anari MR, Sanchez RI, Bakhtiar R, Franklin RB, BaiUie TA (2004) Integration of knowledge-based metabolic predictions with liquid chromatography data-dependent tandem mass spectrometry for drug metabolism studies application to studies on the biotransformation of indinavir. Anal Chem 76(3) 823-832. doi 10.1021/ac034980s Andreozzi R, Raffaele M, Nicklas P (2003) Pharmaceuticals in STP effluents and their solar photodegradation in aquatic environment. Chemosphere 50(10) 1319-1330. doi 10.1016/ 80045-6535(02)00769-5... 

To detect TDG, TDG sulfoxide, and their acid-labile esters, Black and Read (1991) used TiCla reduction, converting these products into single anal5de TDG. TDG was then converted to its bis(pentafluorobenzoyl) derivative and quantified by GC-MS using negative ion chemical ionization. TDG sulfoxide could also be extracted directly using solid-phase extraction, followed by a Florisil cleanup. Derivatization and quantification was conducted as described previously. TiCls was also used by Daly and O Hehir (2007) to reduce the p-lyase pathway biotransformation product l,l-sulphonylbis[2-(methylsulfinyl)ethane] to l,l -sulfonylbis[2-(methylthio) ethane] (SBMTE). This was followed by automated solid-phase extraction and LC-positive ion-ESI-tandem mass spectrometry. 

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