Tandem mass spectrometry selected-reaction monitoring

Selected Reaction Monitoring (SRM) Data acquired from specific product ions corresponding to m/z selected precursor ions recorded via two or more stages of mass spectrometry. Selected reaction monitoring can be preformed as tandem mass spectrometry in time or tandem mass spectrometry in space. The term multiple reaction monitoring is deprecated [1],... 

Because it uses two consecutive mass spectrometers, selected reaction monitoring is also called tandem mass spectrometry or mass spectrometry-mass spectrometry, or just MS-MS. 

Tian, Q. et al., Screening for anthocyanins using high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry with precursor-ion analysis, product-ion analysis, common-neutral-loss analysis, and selected reaction monitoring, J. Chromatogr. A, 1091, 72, 2005. 

Moritz, T. Olsen, J.E. Comparison Between High-Resolution Selected Ion Monitoring, Selected Reaction Monitoring, and Four-Sector Tandem Mass Spectrometry in Quantitative Analysis of Gib-berellins in Milligram Amounts of Plant Tissue. Anal. Chem. 1995, 67, 1711-1716. 

King, R. C., Gundersdorf, R., and Femandez-Metzler, C. L. (2003). Collection of selected reaction monitoring and full scan data on a time scale suitable for target compound quantitative analysis by liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass Spectrom. 17 2413-2422. 

A selective, sensitive, and rapid hydrophilic interaction liquid chromatography with electrospray ionization tandem mass spectrometry was developed for the determination of donepezil in human plasma [32], Donepezil was twice extracted from human plasma using methyl-ferf-butyl ether at basic pH. The analytes were separated on an Atlantis HILIC Silica column with the mobile phase of acetonitrile ammonium formate (50 mM, pH 4.0) (85 15, v/v) and detected by tandem mass spectrometry in the selective reaction monitoring mode. The calibration curve was linear (r = 0.9994) over the concentration range of 0.10-50.0 ng/ ml and the lower limit of quantification was 0.1 ng/ml using 200 /d plasma sample. The CV and relative error for intra- and inter-assay at four quality control levels were 2.7% to 10.5% and —10.0% to 0.0%, respectively. There was no matrix effect for donepezil and cisapride. The present method was successfully applied to the pharmacokinetic study of donepezil after oral dose of donepezil hydrochloride (10 mg tablet) to male healthy volunteers. 

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed [33] and validated for the determination of donepezil in human plasma samples. Diphenhydramine was used as the IS. The collision-induced transition m/z 380 > 91 was used to analyze donepezil in selected reaction monitoring mode. The signal intensity of the m/z 380 —> 91 transition was found to relate linearly with donepezil concentrations in plasma from 0.1 to 20.0 ng/ml. The lower limit of quantification of the LC/MS/MS method was 0.1 ng/ml. The intra- and inter-day precisions were below 10.2% and the accuracy was between 2.3% and +2.8%. The validated LC/MS/MS method was applied to a pharmacokinetic study in which healthy Chinese volunteers each received a single oral dose of 5 mg donepezil hydrochloride. The non-compartmental pharmacokinetic model was used to fit the donepezil plasma concentration-time curve. Maximum plasma concentration was... 

Macek et al. [120] developed a method to quantitate omeprazole in human plasma using liquid chromatography-tandem mass spectrometry. The method is based on the protein precipitation with acetonitrile and a reversed-phase liquid chromatography performed on an octadecylsilica column (55 x 2 mm, 3 /im). The mobile phase consisted of methanol-10 mM ammonium acetate (60 40). Omeprazole and the internal standard, flunitra-zepam, elute at 0.80 0.1 min with a total rim time 1.35 min. Quantification was through positive-ion made and selected reaction monitoring mode at m/z 346.1 —> 197.9 for omeprazole and m/z 314 —> 268 for flunitrazepam, respectively. The lower limit of quantification was 1.2 ng/ml using 0.25 ml of plasma and linearity was observed from 1.2 to 1200 ng/ml. The method was applied to the analysis of samples from a pharmacokinetic study. 

Gschwend MH, Arnold P, Ring J, Martin W (2006) Selective and sensitive determination of amisulpride in human plasma by liquid chromatography-tandem mass spectrometry with positive electrospray ionisation and multiple reaction monitoring. J Chromatogr B Analyt Technol Biomed Life Sci 831(1-2) 132-139. doi S1570-0232(05)00890-l [pii] 10.1016/j.jchromb.2005.11.042... 

At about the same time, our laboratory has reported the development and validation of an LC tandem MS assay for as much as six TKIs simultaneously. The proposed LC-MS/MS method allows the simultaneous determination of clinically relevant ranges of concentrations for the six major TKIs currently in use imatinib, dasatinib, nilotinib, sunitinib, sorafenib, and lapatinib [122], Plasma is purified by acetonitrile protein precipitation followed by reversed-phase chromatographic separation. Analyte quantification is performed by electrospray ionization-triple quadrupole mass spectrometry by selected reaction monitoring (SRM) detection using the positive mode. This was the first broad-range LC-MS/MS assay covering the major currently in-use TKIs. 

Fig. 5 Statistical evaluation of LC-MS-based methods for tropane alkaloids referred in this chapter. (a) Relative frequency of ionization methods. +APCI positive atmospheric pressure chemical ionization, +ESI positive electrospray ionization, FAB fast atom bombardment, +TSP positive thermospray, (b) Relative frequency of scan modes used. MS full scan MS, MS/MS tandem mass spectrometry (product ion scan), MRM multiple reaction monitoring, SIM selected ion monitoring, (c) Relative frequency of mass analysers used. EBQtQ2 double focusing sector field mass spectrometer, IT ion trap, QqQ triple quadrupole, SQ single quadrupole. Considered publications were found by PubMed data-based search and references cited in these articles...

K. A. Francesconi, S. A. Pergantis, Application of selected reaction monitoring tandem mass spectrometry to the quantitative determination of an arsenic-containing nucleoside in a crude biological extract, Analyst, 129 (2004), 398-399. 

The use of selected reaction monitoring (SRM) methods for quantitative bioanalysis represents increased dimensions of mass spectrometry analysis. A SRM method that features a tandem quadrupole MS/MS instrument for the quantitative analysis of an antipsychotic agent, clozapine, in human plasma was recently described by Dear et al. l Preclinical development studies of clozapine in rats and dogs used HPLC with fluorescence detection (FLD). With this method, a better limit of quantitation (LOQ) of Ing/ml was obtained. As the compound moved into the clinical stages of development, a more sensitive method of... 

Quantitation of drags and their metabolites in biological matrices currently is one of the most important applications of LC-MS. This can be attributed to the greatly enhanced selectivity and reliability of the analysis, as compared to LC-UV. Selective reaction monitoring (SRM) in tandem mass spectrometry (MS-MS) has become the method-of-choice in quantitative bioanalysis. Ample examples are described in literatnre. Even a larger number of successful examples are hidden in the archives of pharmaceutical companies and contract research organizations. 

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