Internal tandem mass spectrometry

Residues of isoxaflutole, RPA 202248 and RPA 203328 are extracted from surface water or groundwater on to an RP-102 resin solid-phase extraction (SPE) cartridge, then eluted with an acetonitrile-methanol solvent mixture. Residues are determined by liquid chromatography/tandem mass spectrometry (LC/MS/MS) on a Cg column. Quantitation of results is based on a comparison of the ratio of analyte response to isotopically labeled internal standard response versus analyte response to internal standard response for calibration standards. 

In most cases, ion activation in the reaction region or fragmentation zone is applied to increase the internal energy of the ions transmitted from the ion source. The most common means of ion activation in tandem mass spectrometry is collision-induced dissociation. CID uses gas-phase collisions between the ion and neutral target gas (such as helium, nitrogen or argon) to cause internal excitation of the ion and subsequent dissociation... 

Fig. 11.16. Representation of three tandem mass spectrometry (MS/MS) scan modes illustrated for a triple quadrupole instrument configuration. The top panel shows the attributes of the popular and prevalent product ion CID experiment. The first mass filter is held at a constant m/z value transmitting only ions of a single mlz value into the collision region. Conversion of a portion of translational energy into internal energy in the collision event results in excitation of the mass-selected ions, followed by unimolecular dissociation. The spectrum of product ions is recorded by scanning the second mass filter (commonly referred to as Q3 ). The center panel illustrates the precursor ion CID experiment. Ions of all mlz values are transmitted sequentially into the collision region as the first analyzer (Ql) is scanned. Only dissociation processes that generate product ions of a specific mlz ratio are transmitted by Q3 to the detector. The lower panel shows the constant neutral loss CID experiment. Both mass analyzers are scanned simultaneously, at the same rate, and at a constant mlz offset. The mlz offset is selected on the basis of known neutral elimination products (e.g., H20, NH3, CH3COOH, etc.) that may be particularly diagnostic of one or more compound classes that may be present in a sample mixture. The utility of the two compound class-specific scans (precursor ion and neutral loss) is illustrated in Fig. 11.17.

Jemal, M., Schuster, A., and Whigan, D. B. (2003). Liquid chromatography/tandem mass spectrometry methods for quantitation of mevalonic acid in human plasma and urine method validation, demonstration of using a surrogate analyte, and demonstration of unacceptable matrix effect in spite of use of a stable isotope analog internal standard. Rapid Commun. Mass Spectrom. 17, 1723-1734. 

Liang, H.R. Foltz, R.L. Meng, M. Bennett, P. Ionization enhancement in atmospheric pressure chemical ionization and suppression in electrospray ionization between target drugs and stable-isotope-labeled internal standards in quantitative liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass Spectrom. 2003, 17, 2815—2821. 

Clarke, D.B., Lloyd, A.S., Botting, N.P., Oldfield, M.F., Needs, P.W., and Wiseman, H., Measurement of intact sulfate and glucuronide phytoestrogen conjugates in human urine using isotope dilution liquid chromatography-tandem mass spectrometry with [13C(3)]isoflavone internal standards, Anal. Biochem., 309, 158, 2002. 

Table 2.1.3 Multiple reaction monitoring of amino acids for their tandem mass spectrometry quantitation. In daily practise not all mentioned amino acids are measured in one run, but a set of ten dedicated evaluation programs has been developed, covering groups of amino acids associated with groups of disorders. Amino acids presented in italics indicate stable-isotope-labeled internal standards ... 

Fig. 2.1.1 Tandem mass spectrometry analyses of plasma phenylalanine (phe) and tyrosine (tyr) in a patient with phenylketonuria (PKU left panel phe 793 pmol/1, tyr 70 pmol/1) and in a control (right panel phe 27 pmol/1, tyr 28 pmol/1). The stable-isotope-labelled internal standards are D4-tyrosine (D4-tyr), containing four deuterium atoms and D5-phenylalanine (D5-phe), which has five deuterium atoms.

Samples of 50 pi plasma, standard or control plasma, 20 pi internal standard and 10 pi dithiothreitol solution are thoroughly mixed (vortex) in 1-ml Eppendorf tubes. The tubes are left to stand at room temperature for 15 min. Samples are then depro-teinised by the addition of 500 pi deproteinising acetonitrile solution, with thorough vortex mixing followed by centrifugation at 14,000 rpm (11,000 x g) for 5 min (4°C). Tandem mass spectrometry analysis is performed on 200 pi of the supernatant reserved in appropriate vials. If the analysis is not performed immediately, samples can be stored at -20°C until analysis. 

AdoMet and AdoHcy are separated by HPLC and analysed by electrospray ionisation-tandem mass spectrometry. Quantification is based on comparison of the signal from natural AdoMet (transition m/z 399 ->- m/z 250) and AdoHcy (transition m/z 385 ->- m/z 135 and 134) with that from analogous transitions of the stable isotope internal standards. 

Fig. 2.4.3 Tandem mass spectrometry analysis of pipecolic acid in plasma and the internal standard 2H9-pipecolic acid. Both substances elute at approximately 6.9 min...

Lanckmans, K., Sane, S., Smolders, I., and Michotte, Y. (2007). Use of a structural analogue versus a stable isotope labeled internal standard for the quantification of angiotensin IV in rat brain dialysates using nano-liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass Spectrom. 21 1187-1195. 

L. P. Brull, V. Kovacik, J. Thomas-Oates, J. Haverkamp, and W. Heerma, Sodium-cationized oligosaccharides do not appear to undergo internal residue loss rearrangement processes on tandem mass spectrometry, Rapid Commun. Mass Spectrom., 12 (1998) 1520-1532. 

AT, o-HAT, p-HAT (acid and lactone form) Human serum Positive ion electrospray tandem mass spectrometry LOQ 0.5 ng/ml HPLC-ESI-MS deuterium labeled analog was used as internal standard... 

Abbreviations AM, amlodipine AT, atorvastatin DS, diclofenac sodium EZ, ezetimibe FB, fenofibrate HAT, hydroxy atorvastatin IS, internal standard o-HAT, ortfio-hydroxy atorvastatin p-HAT, para-hydroxy atorvastatin HPLC-ESI-MS, high-performance liquid chromatography with electrospray tandem mass spectrometry LV, lovastatin NA, nicotinic acid NB, novobiocin FV, pravastatin RV, rosuastatin SV, simvastatin RT, roxethromycin UPLC, ultra performance liquid chromatography. 

R.V.S. Nirogi, V.N. Kandikere, M. Shukla, K. Mudigonda, S. Maurya, R. Boosi, Simultaneous quantification of atorvastatin and active metabolites in human plasma by liquid chromatography-tandem mass spectrometry using rosuvastatin as internal standard, Biomed. Chromatogr. 20 (2006) 924—936. 

Stenhoff et al. [117] determined enantiomers of omeprazole in blood plasma by normal-phase liquid chromatography and detection by atmospheric-pressure ionization tandem mass spectrometry. The enantioselec-tive assay of omeprazole is using normal-phase liquid chromatography on a Chiralpak AD column and detection by mass spectrometry. Omeprazole is extracted by a mixture of dichloromethane and hexane and, after evaporation, redissolution and injection, separated into its enantiomers on the chiral stationary phase. Detection is made by a triple quadrupole mass spectrometer, using deuterated analogs and internal standards. The method enables determination in plasma down to 10 nmol/1 and shows excellent consistency suited for pharmacokinetic studies in man. 

Martens-Lobenhoffer et al. [119] used chiral HPLC-atmospheric pressure photoionization tandem mass-spectrometric method for the enantio-selective quantification of omeprazole and its main metabolites in human serum. The method features solid-phase separation, normal phase chiral HPLC separation, and atmospheric pressure photoionization tandem mass spectrometry. The internal standards serve stable isotope labeled omeprazole and 5-hydroxy omeprazole. The HPLC part consists of Agilent 1100 system comprising a binary pump, an autosampler, a thermo-stated column component, and a diode array UV-VIS detector. The enantioselective chromatographic separation took place on a ReproSil Chiral-CA 5 ym 25 cm x 2 mm column, protected by a security guard system, equipped with a 4 mm x 2-mm silica filter insert. The analytes were detected by a Thermo Scientific TSQ Discovery Max triple quadrupole mass spectrometer, equipped with an APPI ion source with a... 

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. 

Song and Naidong [129] analyzed omeprazole and 5-hydroxyomepra-zole in human plasma using hydrophilic interaction chromatography with tandem mass spectrometry. Omeprazole and its metabolite 5-hydroxy omeprazole and the internal standard desoxyomeprazole were extracted from 0.05 ml of human plasma using 0.5 ml of ethyl acetate in a 96-well plate. A portion (0.1 ml) of the ethyl acetate extract was diluted with 0.4 ml of acetonitrile and 10 /il was injected onto a Betasil silica column (5 cm x 3 mm, 5 /rm) and detected by atmospheric pressure ionization 3000 and 4000 with positive electrospray ionization. Mobile phase with linear gradient elution consists of acetonitrile, water, and formic acid (from 95 5 0.1 to 73.5 26.5 0.1 in 2 min). The flow-rate was 1.5 ml/min with total rim time of 2.75 min. The method was validated for a low limit of quantitation at 2.5 ng/ml for both analytes. The method was also validated for specificity, reproducibility, stability, and recovery. 

O Halloran S, Ilett KF (2008) Evaluation of a deuterium-labeled internal standard for the measurement of sirolimus by high-throughput HPLC electrospray ionization tandem mass spectrometry. Clin Chem 54 1386-1389... 

Li C, Ji Z, Nan F et al (2002) Liquid chromatography/tandem mass spectrometry for the determination of fluoxetine and its main active metabolite norfluoxetine in human plasma with deuterated fluoxetine as internal standard. Rapid Commun Mass Spectrom 16 1844-1850... 

Anticancer Drug) in Human Plasma and Urine by Liquid-Liquid Extraction and High-Performance Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry, Using a Deuterated Internal Standard. . 613... 

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