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Selected Reaction Monitoring (selected + reaction_monitoring)
Selected AbstractsDevelopment of a liquid chromatography/tandem mass spectrometry assay for the quantification of rabeprazole in human plasmaRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 16 2005Jinchang Huang A simple and sensitive liquid chromatography/tandem mass spectrometry method, employing electrospray ionization, has been developed and validated to quantify rabeprazole in human plasma using omeprazole as the internal standard. The method was validated to demonstrate the specificity, lower limit of quantification, accuracy, and precision of measurements. Selected reaction monitoring was specific for rabeprazole and omeprazole (the internal standard, IS); no endogenous materials interfered with the analysis of rabeprazole and IS from blank plasma. The assay was linear over the concentration range 0.2,200,ng/mL using a 2,µL aliquot of plasma. The correlation coefficients for the calibration curves ranged from 0.9988,0.9994. The intra- and inter-day precision, calculated from quality control samples, were less than 6.65%. A mixture of methanol and water (50:50) was used as the isocratic mobile phase, with 0.1% of formic acid in water, that did not affect the stability of rabeprazole or IS. A simple sample preparation method of protein precipitation with methanol was chosen. The method was employed in a pharmacokinetic study after oral administration of 20,mg rabeprazole to 24 healthy volunteers. Copyright © 2005 John Wiley & Sons, Ltd. [source] Simultaneous determination of honokiol and magnolol in Magnolia officinalis by liquid chromatography with tandem mass spectrometric detectionBIOMEDICAL CHROMATOGRAPHY, Issue 10 2006Yu-Tse Wu Abstract An optimized high-performance liquid chromatographic method coupled with tandem mass spectrometric detection (LC-MS/MS) was developed for the simultaneous determination of honokiol and magnolol in Magnolia officinalis. Honokiol and magnolol were separated from the extracts using a reversed-phase C18 column with a mobile phase consisted of acetonitrile and water (75:25, v/v) at a flow-rate of 0.8 mL/min. Selected reaction monitoring (SRM) mode was used for all sample quantification by the precursor-ion/product ion pair m/z 265 , m/z 224 for honokiol and m/z 265 , m/z 247 for magnolol. Validation data showed that this method has good linearity (r2 > 0.995) over the concentration range of 0.0025,0.5 µg/mL for honokiol and magnolol, and both intra- and inter-day variability were acceptable within 15% at the lowest concentrations for this method. This proposed method provides excellent specificity, higher sensitivity and shorter run time than conventional methods and was applied successfully to determine the contents of honokiol and magnolol in M. officinalis. Copyright © 2006 John Wiley & Sons, Ltd. [source] Qualitative study of in vivo melphalan adduct formation in the rat by miniaturized column-switching liquid chromatography coupled with electrospray mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2004Bart Van den Driessche Abstract In a general study of DNA adduct formation with melphalan, rats were intravenously injected with a single high dose (10 mg kg,1). Adduct formation was studied at the nucleoside level in the target organs liver, bone marrow, kidney and blood with the use of 2D liquid chromatography/tandem mass spectrometry (LC/MS/MS). Adducts of dGuo and dAdo were detected under selected reaction monitoring in liver and bone marrow 10 h after administration of melphalan. In the DNA hydrolysates from kidney and blood a Gua,melphalan adduct was found, although in very low abundance. These first results of the search for in vivo -formed melphalan adducts in the rat showed that our miniaturized LC/MS technique is useful for investigating this type of compound. More experiments will be performed in this area to gather more information about the pharmacokinetics and the quantity of adducts formed. Copyright © 2003 John Wiley & Sons, Ltd. [source] Development of a targeted adductomic method for the determination of polycyclic aromatic hydrocarbon DNA adducts using online column-switching liquid chromatography/tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 16 2010Rajinder Singh Human exposure to polycyclic aromatic hydrocarbons (PAHs) from sources such as industrial or urban air pollution, tobacco smoke and cooked food is not confined to a single compound, but instead to mixtures of different PAHs. The interaction of different PAHs may lead to additive, synergistic or antagonistic effects in terms of DNA adduct formation and carcinogenic activity resulting from changes in metabolic activation to reactive intermediates and DNA repair. The development of a targeted DNA adductomic approach using liquid chromatography/tandem mass spectrometry (LC/MS/MS) incorporating software-based peak picking and integration for the assessment of exposure to mixtures of PAHs is described. For method development PAH-modified DNA samples were obtained by reaction of the anti- dihydrodiol epoxide metabolites of benzo[a]pyrene, benzo[b]fluoranthene, dibenzo[a,l]pyrene (DB[a,l]P) and dibenz[a,h]anthracene with calf thymus DNA in vitro and enzymatically hydrolysed to 2,-deoxynucleosides. Positive LC/electrospray ionisation (ESI)-MS/MS collision-induced dissociation product ion spectra data showed that the majority of adducts displayed a common fragmentation for the neutral loss of 116 u (2,-deoxyribose) resulting in a major product ion derived from the adducted base. The exception was the DB[a,l]P dihydrodiol epoxide adduct of 2,-deoxyadenosine which resulted in major product ions derived from the PAH moiety being detected. Specific detection of mixtures of PAH-adducted 2,-deoxynucleosides was achieved using online column-switching LC/MS/MS in conjunction with selected reaction monitoring (SRM) of the [M+H]+ to [M+H,116]+ transition plus product ions derived from the PAH moiety for improved sensitivity of detection and a comparison was made to detection by constant neutral loss scanning. In conclusion, different PAH DNA adducts were detected by employing SRM [M+H,116]+ transitions or constant neutral loss scanning. However, for improved sensitivity of detection optimised SRM transitions relating to the PAH moiety product ions are required for certain PAH DNA adducts for the development of targeted DNA adductomic methods. Copyright © 2010 John Wiley & Sons, Ltd. [source] Feasibility of capillary liquid chromatography/microchip atmospheric pressure photoionization mass spectrometry in analyzing anabolic steroids in urine samplesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 7 2010Linda L. Ahonen We examined the feasibility of capillary liquid chromatography/microchip atmospheric pressure photoionization tandem mass spectrometry (capLC/µAPPI-MS/MS) for the analysis of anabolic steroids in human urine. The urine samples were pretreated by enzymatic hydrolysis (with , -glucuronidase from Helix pomatia), and the compounds were liquid-liquid extracted with diethyl ether. After separation the compounds were vaporized by microchip APPI, photoionized by a 10,eV krypton discharge lamp, and detected by selected reaction monitoring. The capLC/µAPPI-MS/MS method showed good sensitivity with detection limits at the level of 1.0,ng,mL,1, good linearity with correlation coefficients between 0.9954 and 0.9990, and good repeatability with relative standard deviations below 10%. These results demonstrate that microchip APPI combined with capLC/MS/MS provides a new potential method for analyzing non-polar and neutral compounds in biological samples. Copyright © 2010 John Wiley & Sons, Ltd. [source] Multi-residue analysis of eight thioamphetamine designer drugs in human urine by liquid chromatography/tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 19 2009Maria Nieddu An analytical procedure for the simultaneous determination in human urine of several thioamphetamine designer drugs (2C-T and ALEPH series) is reported. The quantitative analysis was performed by liquid chromatography/tandem mass spectrometry and has been fully validated. The mass spectrometer was operated in positive-ion, selected reaction monitoring (SRM) mode. In order to minimize interferences with matrix components and to preconcentrate target analytes, solid-phase extraction was introduced in the method as a clean-up step. The entire method was validated for selectivity, linearity, precision and accuracy. The method turned out to be specific, sensitive, and reliable for the analysis of amphetamine derivatives in urine samples. The calibration curves were linear over the concentration range of 1 to 100,ng,mL,1 for all drugs with correlation coefficients that exceeded 0.996. The lower limits of detection (LODs) and quantification (LOQs) ranged from 1.2 to 4.9,ng,mL,1 and from 3.2 to 9.6,ng,mL,1, respectively. Copyright © 2009 John Wiley & Sons, Ltd. [source] Electrospray ionisation with selected reaction monitoring for the determination of Mn-citrate, Fe-citrate, Cu-citrate and Zn-citrateRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 15 2009Volker Nischwitz Citrate complexes of Mn and Fe, and potentially those of Cu and Zn, are considered as important low molecular mass species in human serum and cerebrospinal fluid (CSF). For example, Mn is supposed to enter the brain under excess exposure as Mn-citrate leading to neurotoxic effects. Mn-citrate has been characterised in human CSF using chromatography and electrophoresis online with inductively coupled plasma mass spectrometry, but not yet with molecular mass spectrometry. Therefore, this study explores the potential of electrospray ionisation (ESI) with selected reaction monitoring (SRM) for the detection of metal-citrate complexes, in particular Mn-citrate. The collision-induced dissociation of precursor ions with various metal:citrate stoichiometries was studied for Mn-citrate, Fe-citrate, Cu-citrate and Zn-citrate. High selectivity was achieved for Mn(II)-citrate even in respect to Fe(III)-citrate which forms isobaric precursor ions. The limit of detection for Mn-citrate was estimated to be around 250,µg,L,1 (referring to the total Mn content in the standard) using flow injection. The sensitivity was sufficient for the determination of Mn-citrate in standard solutions and in an extract of an Mn-citrate-containing supplement. An improved ESI source design is expected to reduce the limits of detection significantly. The developed ESI-SRM method has the potential to provide complementary data for the quality control of current separation methods for metal citrates using element-selective detection, with application to biomedical samples and further matrices. Copyright © 2009 John Wiley & Sons, Ltd. [source] Phospholipids in liquid chromatography/mass spectrometry bioanalysis: comparison of three tandem mass spectrometric techniques for monitoring plasma phospholipids, the effect of mobile phase composition on phospholipids elution and the association of phospholipids with matrix effectsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 14 2009Yuan-Qing Xia Because plasma phospholipids may cause matrix effects in bioanalytical liquid chromatography/tandem mass spectrometry (LC/MS/MS) methods, it is important to establish optimal mass spectrometric techniques to monitor the fate of phospholipids during method development and application. We evaluated three MS/MS techniques to monitor phospholipids using positive and negative electrospray ionization (ESI). The first technique is based on using positive precursor ion scan of m/z 184, positive neutral loss scan of 141 Da and negative precursor ion scan of m/z 153. The second technique is based on using class-specific positive and negative selected reaction monitoring (SRM) transitions to monitor class-representative phospholipids. The third technique, previously reported, utilizes in-source collision-induced dissociation (CID)-based positive SRM of m/z 184,,,184. We recommend the all-inclusive technique 1 for use in qualitative assessment of all classes of phospholipids and technique 2 for use in quantitative assessment of class-representative phospholipids. Secondly, we evaluated the elution behaviors of the plasma phospholipids under different reversed-phase mobile phase conditions. The phospholipid-eluting strength of a mobile phase was mainly dependent on the type and amount (%) of the organic eluent and the strength increased in the order of methanol, acetonitrile and isopropyl alcohol. Under the commonly used gradient and isocratic elution schemes in LC/MS/MS bioanalysis, not all the phospholipids are eluted off the column. Thirdly, we investigated the association between phospholipids and matrix effects in positive and negative ESI using basic, acidic and neutral analytes. While the phospholipids caused matrix effects in both positive and negative ESI, the extent of ionization suppression was analyte-dependent and was inversely related to the retention factor and broadness of the phospholipids peaks. The lysophospholipids which normally elute earlier in reversed-phase chromatography are more likely to cause matrix effects compared to the later-eluting phospholipids in spite of the larger concentrations of the latter in plasma. Copyright © 2009 John Wiley & Sons, Ltd. [source] A reliable analytical approach based on gas chromatography coupled to triple quadrupole and time-of-flight mass analyzers for the determination and confirmation of polycyclic aromatic hydrocarbons in complex matrices from aquaculture activitiesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 13 2009Jaime Nácher-Mestre The potential of gas chromatography coupled to tandem mass spectrometry (GC/MS/MS) with a triple quadrupole analyzer (QqQ) has been investigated for the quantification and reliable identification of sixteen polycyclic aromatic hydrocarbons (PAHs) from the EPA priority list in animal and vegetable samples from aquaculture activities, whose fat content ranged from 5 to 100%. Matrices analyzed included fish fillet, fish feed, fish oil and linseed oil. Combining optimized saponification and solid-phase extraction led to high efficiency in the elimination of interfering compounds, mainly fat, from the extracts. The developed procedure minimized the presence of these interfering compounds in the extracts and provided satisfactory recoveries of PAHs. The excellent sensitivity and selectivity of GC/(QqQ)MS/MS in selected reaction monitoring (SRM) allowed to reach limits of detection at pg/g levels. Two SRM transitions were acquired for each analyte to ensure reliable identification of compounds detected in samples. Confirmation of positive findings was performed by GC coupled to high-resolution time-of-flight mass spectrometry (GC/TOFMS). The accurate mass information provided by GC/TOFMS in full acquisition mode together with its high mass resolution makes it a powerful analytical tool for the unequivocal confirmation of PAHs in the matrices tested. The method developed was applied to the analysis of real-world samples of each matrix studied with the result of detecting and confirming the majority of analytes at the µg/kg level by both QqQ and TOF mass spectrometers. Copyright © 2009 John Wiley & Sons, Ltd. [source] A liquid chromatography/tandem mass spectrometric approach for the determination of gangliosides GD3 and GM3 in bovine milk and infant formulaeRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 24 2006Lambert K. Sřrensen A liquid chromatographic/tandem mass spectrometric method using pneumatically assisted electrospray ionisation (LC/ESI-MS/MS) was developed for the determination of gangliosides GD3 and GM3 in milk and infant formulae. The gangliosides were extracted in a chloroform/methanol/water environment and cleaned up by solid-phase extraction (SPE) on an end-capped C8 sorbent. The gangliosides were detected in negative ion mode after separation on a reversed-phase (RP) C5 analytical column. From the different ganglioside molecular species, product ions at m/z 290 corresponding to an N-acetylneuraminic acid fragment were produced in the collision cell and used in selected reaction monitoring. A standard addition technique was applied for quantification. The relative repeatability standard deviations were less than 5% for GD3 (level 10,mg/L) and 14% for GM3 (level 0.1,0.2,mg/L). Copyright © 2006 John Wiley & Sons, Ltd. [source] Increased productivity in quantitative bioanalysis using a monolithic column coupled with high-flow direct-injection liquid chromatography/tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 11 2006Mike-Qingtao Huang The feasibility of using a monolithic column as the analytical column in conjunction with high-flow direct-injection liquid chromatography/tandem mass spectrometry (LC/MS/MS) to increase productivity for quantitative bioanalysis has been investigated using plasma samples containing a drug and its epimer metabolite. Since the chosen drug and its epimer metabolite have the same selected reaction monitoring (SRM) transitions, chromatographic baseline separation of these two compounds was required. The results obtained from this monolithic column system were directly compared with the results obtained from a previously validated assay using a conventional C18 column as the analytical column. Both systems have the same sample preparation, mobile phases and MS conditions. The eluting flow rate for the monolithic column system was 3.2,mL/min (with 4:1 splitting) and for the C18 column system was 1.2,mL/min (with 3:1 splitting). The monolithic column system had a run time of 5,min and the conventional C18 column system had a run time of 10,min. The methods on the two systems were found to be equivalent in terms of accuracy, precision, sensitivity and chromatographic separation. Without sacrificing the chromatographic separation, sensitivity, accuracy and precision of the method, the reduced run time of the monolithic column method increased the sample throughput by a factor of two. Copyright © 2006 John Wiley & Sons, Ltd. [source] Development of a low volume plasma sample precipitation procedure for liquid chromatography/tandem mass spectrometry assays used for drug discovery applicationsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 15 2005Xiaoying Xu The demand for high sensitivity bioanalytical methods has dramatically increased in the drug discovery stage; in addition, there has been a growing trend of reducing the sample volume that is required for these assays. A sensitive high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) procedure has been developed and tested to meet these needs. The assay requires only a low plasma sample volume (10,µL) and employs a protein precipitation procedure using a 1:6 plasma/acetonitrile ratio. The supernatant is injected directly into the LC/MS/MS system using the selected reaction monitoring (SRM) procedure for detection. A generic HPLC gradient based on a methanol/water mobile phase with a flow rate set to 0.8,mL/min was used. The test method showed very good linearity between 0.1,1000,ng/mL (R2,=,0.9737), precision (%RSD,=,6,9), accuracy (%RE,=,,2) and reproducibility (%RSD,=,11). A drug discovery IV/PO study was assayed using both the new low volume method and our standard volume (50,µL) method. The correlation of the two sets of data from the two methods was excellent (R2,=,0.9287). This new assay procedure has been successfully used in our laboratory for over 100 different rat or mouse discovery PK studies. Copyright © 2005 John Wiley & Sons, Ltd. [source] A strategy for quantitative bioanalysis of non-polar neutral compounds by liquid chromatography/electrospray ionization tandem mass spectrometry: determination of TS-962, a novel acyl-CoA:cholesterol acyltransferase inhibitor, in rabbit aorta and liver tissuesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 8 2001Jun-ichi Yamaguchi A strategy for the sensitive and reliable quantitative determination of non-polar neutral compounds in biological matrices by liquid chromatography/electrospray ionization tandem mass spectrometry is described in the context of assay development for TS-962, a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, in rabbit aorta and liver tissues. The electrospray ionization (ESI) mass spectrum of this compound with a mobile phase of water/acetonitrile did not give abundant [M,+,H]+ ions, but did give alkali metal cation adducts such as [M,+,Na]+, [M,+,CH3CN,+,Na]+ and [M,+,K]+ ions. The cationized species are acknowledged as unsuitable precursor ions for selected reaction monitoring (SRM) for various reasons, such as difficulty in obtaining characteristic product ions in low-energy collision-induced dissociation, and irreproducibility of the adduct-ion intensities. To overcome this problem, a solution of 3.4,mM trifluoroacetic acid in 2-propanol was added to the mobile phase as a postcolumn additive, resulting in a decrease of the undesirable adduct formation and significant enhancement of [M,+,H]+ ion intensity. An attempt was then made to prevent the matrix effect by employing a column-switching system, which allowed direct injection of a large volume of 2-propanolic tissue homogenate (950,µL) followed by sufficient clean-up, separation, and ESI-SRM on-line. This enabled development of a sensitive and reliable assay method for TS-962 in rabbit aorta and liver tissues in the concentration range of 5,500,ng/g wet tissue using a 25-mg aliquot of tissue sample. Application of this method to the determination of aortic TS-962 levels at 24,h after repeated oral administration of this compound (3,mg/kg) once a day for 12 weeks to 1% cholesterol-fed rabbits is also presented. Results showed that TS-962 is well distributed to both the thoracic and abdominal aorta tissues, at levels higher than the 50% inhibitory concentration value of this compound for microsomal ACAT activity from rabbit aorta. Copyright © 2001 John Wiley & Sons, Ltd. [source] | ||||||||||