Chemical Ionization Mass Spectrometric Detection Research Articles

Quantification of trace fatty acid methyl esters in diesel fuel by using multidimensional gas chromatography with electron and chemical ionization mass spectrometry.

Measurement of contamination of marine and naval diesel fuels (arising from product mixing or adulteration) with biodiesel or fatty acid methyl esters can be problematic, especially at very low levels. A suitable solution for this task for trace amounts of individual fatty acid methyl esters with resolution and quantification can be achieved by using a multidimensional gas chromatographic approach with electron and chemical ionization mass spectrometric detection. A unique column set comprising a 100 m methyl-siloxane nonpolar first dimension column and high-temperature ionic liquid column in the second dimension enabled identification of individual fatty acid methyl esters at below the lowest concentrations required to be reported in a diesel fuel matrix. Detection limits for individual fatty acid methyl esters compounds ranged from 0.5 to 5.0 mg/L, with excellent linearity up to 5000 mg/L and repeatability of the method from 1.3 to 3.2%. The method was applied to the analysis of diesel fuel samples with suspected biodiesel contamination. Contamination at 568 mg/L was calculated for an unknown sample and interpretation of the results permitted the determination of a likely source of the contamination.

A novel derivatization method for the determination of Fosfomycin in human plasma by liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometric detection via phase transfer catalyzed derivatization

An analytical method employing novel sample preparation and liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometric detection (LC–APCI/MS) was developed for the determination of fosfomycin in human plasma. Sample preparation involves derivatization through phase transfer catalysis (PTC) which offers multiple advantages due to the simultaneous extraction, preconcentration and derivatization of the analyte. Using a PT catalyst, fosfomycin was extracted from plasma in an organic phase and, then converted to a pentafluorobenzyl ester with the use of pentafluorobenzyl bromide (PFBBr) derivatization reagent. The method was fully optimized by taking into account both PTC and derivatization parameters. Several catalysts, in a wide range of concentrations, with different counter ions and polarities were tested along with different extraction solvents and pH values. Thereafter, the derivatization procedure was optimized by altering the amount of the derivatization reagent, the temperature of the reaction and finally, the derivatization duration. As internal standard (I.S.) ethylphosphonic acid was chosen and underwent the same pretreatment. The derivatives were separated on a pentafluorophenyl (PFP)-C18 analytical column, which provides unique selectivity, using an isocratic elution with acetonitrile–water (70–30, v/v). The method was validated according to US Food and Drug Administration (FDA) guidelines and can be used for a bioequivalence study of fosfomycin in human plasma. The correlation coefficient (r2) of the calibration curve of spiked plasma solutions in the range of 50–12000ng/mL was found greater than 0.999 with a limit of quantitation (LOQ) equal to 50ng/ml (for 500μL plasma sample).

Dispersive liquid–liquid microextraction for the determination of vitamins D and K in foods by liquid chromatography with diode-array and atmospheric pressure chemical ionization-mass spectrometry detection

A simple and rapid method was developed using reversed-phase liquid chromatography (LC) with both diode array (DAD) and atmospheric pressure chemical ionization mass spectrometric (APCI-MS) detection, for the simultaneous analysis of the vitamins ergocalciferol (D2), cholecalciferol (D3), phylloquinone (K1), menaquinone-4 (K2) and a synthetic form of vitamin K, menadione (K3). The Taguchi experimental method, an orthogonal array design (OAD), was used to optimize an efficient and clean preconcentration step based on dispersive liquid–liquid microextraction (DLLME). A factorial design was applied with six factors and three levels for each factor, namely, carbon tetrachloride volume, methanol volume, aqueous sample volume, pH of sample, sodium chloride concentration and time of the centrifugation step. The DLLME optimized procedure consisted of rapidly injecting 3mL of acetonitrile (disperser solvent) containing 150µL carbon tetrachloride (extraction solvent) into the aqueous sample, thereby forming a cloudy solution. Phase separation was performed by centrifugation, and the sedimented phase was evaporated with nitrogen, reconstituted with 50µL of acetonitrile, and injected. The LC analyses were carried out using a mobile phase composed of acetonitrile, 2-propanol and water, under gradient elution. Quantification was carried out by the standard additions method. The APCI-MS spectra, in combination with UV spectra, permitted the correct identification of compounds in the food samples. The method was validated according to international guidelines and using a certified reference material. The validated method was applied for the analysis of vitamins D and K in infant foods and several green vegetables. There was little variability in the forms of vitamin K present in vegetables, with the most abundant vitamer in all the samples being phylloquinone, while menadione could not be detected. Conversely, cholecalciferol, which is present in food of animal origin, was the main form in infant foods, while ergocalciferol was not detected.

Quantification of β-carotene, retinol, retinyl acetate and retinyl palmitate in enriched fruit juices using dispersive liquid–liquid microextraction coupled to liquid chromatography with fluorescence detection and atmospheric pressure chemical ionization-mass spectrometry

A detailed optimization of dispersive liquid–liquid microextraction (DLLME) was carried out for developing liquid chromatographic (HPLC) techniques, using both fluorescence and atmospheric pressure chemical ionization mass spectrometric (APCI-MS) detection, for the simultaneous analysis of preforms of vitamin A: retinol (R), retinyl acetate (RA), retinyl palmitate (RP) and β-carotene (β-C). The HPLC analyses were carried out using a mobile phase composed of methanol and water, with gradient elution. The APCI-MS and fluorescence spectra permitted the correct identification of compounds in the analyzed samples. Parameters affecting DLLME were optimized using 2mL of methanol (disperser solvent) containing 150μL carbon tetrachloride (extraction solvent). The precision ranged from 6% to 8% (RSD) and the limits of detection were between 0.03 and 1.4ngmL−1, depending on the compound. The enrichment factor values were in the 21–44 range. Juice samples were analyzed without saponification and no matrix effect was found when using fluorescence detection, so calibration was possible with aqueous standards. However, a matrix effect appeared with APCI-MS, in which case it was necessary to apply matrix-matched calibration. There was great variability in the forms of vitamin A present in the juices, the most abundant ester being retinyl acetate (0.04 to 3.4μgmL−1), followed by the amount of retinol (0.01 to 0.16μgmL−1), while retinyl palmitate was not detected, except in the milk-containing juice, in which RP was the main form. The representative carotenoid β-carotene was present in the orange, peach, mango and multifruit juices in high amounts. The method was validated using two certified reference materials.

Analysis, occurrence, and toxic potential of pyrethroids, and fipronil in sediments from an urban estuary

Eight pyrethroids and fipronil and its three major degradates were analyzed in urban estuarine sediments that exhibited a range of toxic effects to an amphipod test species. Sediments from Ballona Creek, an urban estuary in Southern California (USA), collected during three dry season events were analyzed by gas chromatography with electron capture and negative chemical ionization mass spectrometric detection (GC-ECD and GC-NCI-MS). The two detection methods were in agreement for intermediate levels of pyrethroid contamination (10-50 ng/g dry wt) but deviated for both low and high concentrations (< 5 and > 50 ng/g). Sediments contained total pyrethroids as high as 473 ng/g with permethrin, bifenthrin, and cypermethrin as the most abundant compounds. In contrast, fipronil and its desulfinyl, sulfide, and sulfone degradates were detected at much lower levels (<or= 0.18-16 ng/g). Toxic units estimated for these compounds revealed that bifenthrin and cypermethrin were likely contributors to the mortality observed in tests with the estuarine amphipod Eohaustorius estuarius. Although fipronil was not a likely contributor to the observed mortality, the concentrations detected may be of concern for more sensitive crustacean species. Furthermore, the spatial pattern of pyrethroid contamination and potential toxicity was highly correlated with fine-grained substrate, which shifted to downstream stations within a three-month period during the dry season.

Geographic specificity of Aroclor 1268 in bottlenose dolphins (Tursiops truncatus) frequenting the Turtle/Brunswick River Estuary, Georgia (USA)

Coastal marine resources are at risk from anthropogenic contaminants, including legacy persistent organic pollutants (POPs) with half-lives of decades or more. To determine if polychlorinated biphenyl (PCB) signatures can be used to distinguish among local populations of inshore bottlenose dolphins ( Tursiops truncatus) along the southeastern U.S. coast, blubber from free-ranging and stranded animals were collected along the Georgia coast in 2004 and analyzed for PCB congeners using gas chromatography with electron capture and negative chemical ionization mass spectrometric detection (GC-ECD and GC-NCI-MS). Mean total PCB concentrations (77 ± 34 μg/g lipid) were more than 10 fold higher and congener distributions were highly enriched in Cl 7–Cl 10 homologs in free-ranging animals from the Turtle/Brunswick River estuary (TBRE) compared with strandings samples from Savannah area estuaries 90 km to the north. Using principal components analysis (PCA), the Aroclor 1268 signature associated with TBRE animals was distinct from that observed in Savannah area animals, and also from those in animals biopsied in other southeastern U.S estuaries. Moreover, PCB signatures in dolphin blubber closely resembled those in local preferred prey fish species, strengthening the hypothesis that inshore T. truncatus populations exhibit long-term fidelity to specific estuaries and making them excellent sentinels for assessing the impact of stressors on coastal ecosystem health.

Validation and Application of a GC-MS Method for Determining Soman Concentration in Rat Plasma Following Low-Level Vapor Exposure

A method for determining the chemical warfare agent soman (GD) in rat plasma has been validated and applied to low-level inhalation exposure studies currently being conducted. This method utilizes a fluoride ion-based regeneration assay with isotope dilution followed by large volume injection gas chromatography with ammonia chemical ionization mass spectrometric detection. Following sample preparation by solid phase extraction, chromatographic separation was achieved using a 14% cyanopropylphenyl/86% dimethyl polysiloxane capillary column with a total run time of 18.16 min. Soman and the deuterated isotope ((2)H(4)-soman) internal standard were detected using the selected ion monitoring mode and quantitated using the ammonia adduction ratio of m/z ions 200/204. A reproducible linear relationship was obtained for the quantitative concentration range of 10 pg on-column to 1000 pg on-column (r(2) = 0.9995) for standards in ethyl acetate with a detection limit of 5.65 pg on-column, and an average recovery of 93% in plasma. This sensitive method was successfully applied to the analysis of soman in rat plasma immediately post-exposure, resulting in the construction of dose-response plots.

High temperature to increase throughput in liquid chromatography and liquid chromatography–mass spectrometry with a porous graphitic carbon stationary phase

High separation temperatures in liquid chromatography and liquid chromatography-mass spectrometry with a porous graphitic carbon column were investigated. Separation temperature was varied up to 200 degrees C, and the effect on retention, analysis time, and sensitivity was measured. Analysis times were reduced more than six-fold, whilst baseline resolution was maintained. The impact of the separation temperature on signal-to-noise ratio with atmospheric pressure chemical ionisation or electrospray mass spectrometric detection was also investigated. The potential of using superheated water for the analysis of some very polar compounds is illustrated. Monitoring of column stability detected no loss of performance, due to the highly stable nature of the 100% carbon stationary phase.

Validation and application of a liquid chromatographic–mass spectrometric method for determination of artesunate in pharmaceutical samples

A simple and rapid liquid chromatographic–mass spectrometric assay for the evaluation of artesunate in vials for injection has been developed and validated.The content of each vial was dissolved in 3.0mL of methanol using a SGE analytical syringe (1.0mL). Each sample was diluted to a theoretical concentration of 1000ng/mL and analysed in triplicate. Three replicates of calibration standards at concentrations 500, 1000 and 1500ng/mL were used to construct a calibration curve. Artesunate was analysed by liquid chromatography with atmospheric pressure chemical ionisation (APCI) mass spectrometric (MS) detection on a Hypersil Gold column (100mm×4.6mm) using a mobile phase containing methanol–ammonium acetate 10mM pH 5.3 (70:30, v/v) at a flow rate of 1mL/min. The assay was implemented for the analysis of artesunate for injection purchased from Guilin Pharmaceutical Company in China.

HPLC with Column Switching Coupled to APCI–MS for Pharmacokinetic Study of Amygdalin in Rabbit Plasma

A fast and validated assay was established for the pharmacokinetic study of amygdalin in Armeniacae Semen in rabbit. The method involved column switching (CS) enrichment, separation, post-column derivatization, and atmospheric pressure chemical ionization (APCI) mass spectrometric detection. Plasma sample was enriched by CS using a MAYI-ODS as the first column. Analytes of interest were isolated and analyzed on a second column of Zorbax SB-C18. To detect amygdalin in plasma samples, a T-piece was connected between the HPLC outlet and the APCI source to add a mixture of dichloromethane and methanol to the eluent by an isocratic pump. Calibration graphs showed good linearity over a range of 1.0–1,280 ng mL−1. The detection limit was 0.2 ng mL−1. The intra- and inter-day accuracies were within 3.9%. The method was successfully applied to a study of the pharmacokinetics of amygdalin after an intravenous injection of amygdalin extracts to rabbits with a dose of 400 mg kg−1. The results indicate that amygdalin is a one-compartment open model with a first order absorption phase.

Improved method for the determination of zinc pyrithione in environmental water samples incorporating on-line extraction and preconcentration coupled with liquid chromatography atmospheric pressure chemical ionisation mass spectrometry

A method has been developed for the determination of zinc pyrithione (ZnPT) in environmental water samples using monolithic reversed-phase silica columns for rapid on-line large volume solid phase extraction in tandem with on-line matrix removal using sacrificial strong anion exchange (SAX) columns. This is coupled with reversed-phase liquid chromatography with atmospheric pressure chemical ionisation mass spectrometric detection. Limits of detection in spiked river water samples, using a 200 mL preconcentration volume, were determined as 18 ng L −1, with a limit of quantitation of 62 ng L −1. The percentage recovery from spiked river water was found to be 72 ± 9 ( n = 3 extractions), whilst overall method precision, following 10 repeat complete analyses was found to be 27% RSD at 1 μg L −1. Linearity was determined over the concentration range of 0.25–10 μg L −1 and the calculated regression coefficient was R 2 = 0.9802. The method was used to investigate the environmental fate of zinc pyrithione in waters and its partition coefficient between sediment and water phases.

A fast method for determining low‐molecular‐mass aliphatic carboxylic acids by high‐performance liquid chromatography–atmospheric pressure chemical ionization mass spectrometry

A fast quantitative high-performance liquid chromatographic separation method with atmospheric pressure chemical ionization mass spectrometric detection (HPLC-APCI-MS) was developed for the determination of low-molecular-mass aliphatic mono- and dicarboxylic acids typically present in different industrial process waters. A mixture of glycolic, lactic, a-glucoisosaccharinic, oxalic, maleic, fumaric, succinic, malic, glutaric, methylsuccinic, and adipic acids was separated using an RP chromatographic system. Adipic acid was used as an internal standard to calculate correlation coefficients for the acids studied. The chromatographic analysis of these acids was primarily carried out by means of gradient elution with an aqueous formic acid solution (0.15%, pH 2.5) and methanol using a modified C18 stationary phase. Good acid separation could be obtained for all acids by optimizing the chromatographic conditions. The method provides a simple sample preparation and faster analysis time compared to the traditional gas chromatographic methods, thus enabling almost real-time monitoring of these acids. Finally, the method developed was applied to the analysis of a complex mixture of aliphatic hydroxy carboxylic acids, which are formed as alkaline degradation products of carbohydrates during wood delignification and are present in the cooking spent liquor (black liquor).

Separation of triacylglycerols in a complex lipidic matrix by using comprehensive two‐dimensional liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometric detection

Journal of Separation ScienceVolume 29, Issue 10 p. 1530-1530 ErratumFree Access Separation of triacylglycerols in a complex lipidic matrix by using comprehensive two-dimensional liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometric detection This article corrects the following: A study of surface modification and anchoring techniques used in the preparation of monolithic microcolumns in fused silica capillaries Julien Courtois, Michal Szumski, Emil Byström, Agnieszka Iwasiewicz, Andrei Shchukarev, Knut Irgum, Volume 29Issue 1Journal of Separation Science pages: 14-24 First Published online: January 12, 2006 Paola Dugo, Paola Dugo Dipartimento di Chimica Organica e Biologica, Facoltà di Scienze, Università di Messina, Messina, ItalySearch for more papers by this authorTiina Kumm, Tiina Kumm Dipartimento Farmaco-chimico, Facoltà di Farmacia, Università di Messina, Messina, Italy. Fax: +39-090-6766532Search for more papers by this authorBiagina Chiofalo, Biagina Chiofalo Dipartimento MO.BI.FI.PA., Facoltà di Medicina Veterinaria, Università di Messina, Messina, ItalySearch for more papers by this authorAntonella Cotroneo, Antonella Cotroneo Dipartimento Farmaco-chimico, Facoltà di Farmacia, Università di Messina, Messina, Italy. Fax: +39-090-6766532Search for more papers by this authorLuigi Mondello, Luigi Mondello lmondello@pharma.unime.it Search for more papers by this author Paola Dugo, Paola Dugo Dipartimento di Chimica Organica e Biologica, Facoltà di Scienze, Università di Messina, Messina, ItalySearch for more papers by this authorTiina Kumm, Tiina Kumm Dipartimento Farmaco-chimico, Facoltà di Farmacia, Università di Messina, Messina, Italy. Fax: +39-090-6766532Search for more papers by this authorBiagina Chiofalo, Biagina Chiofalo Dipartimento MO.BI.FI.PA., Facoltà di Medicina Veterinaria, Università di Messina, Messina, ItalySearch for more papers by this authorAntonella Cotroneo, Antonella Cotroneo Dipartimento Farmaco-chimico, Facoltà di Farmacia, Università di Messina, Messina, Italy. Fax: +39-090-6766532Search for more papers by this authorLuigi Mondello, Luigi Mondello lmondello@pharma.unime.it Search for more papers by this author First published: 05 July 2006 https://doi.org/10.1002/jssc.200690041Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume29, Issue10Special Issue: Chromatographic Chiral SeparationsJuly 2006Pages 1530-1530 RelatedInformation

Separation of triacylglycerols in a complex lipidic matrix by using comprehensive two‐dimensional liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometric detection

The present investigation describes the employment of a comprehensive 2-D HPLC system, based on the combination of a silver ion and an RP column, for the characterization of the triacylglycerol (TAG) fraction of a very complex lipidic sample: donkey milk fat. The TAGs were grouped on the resulting bidimensional contour plot according to their double bond numbers (aligned along vertical bands) and according to their partition numbers (aligned along horizontal bands). Peak assignment was supported by using atmospheric pressure chemical ionization mass spectrometric (APCI-MS) detection. The combination of the enhanced resolving power of comprehensive multidimensional LC, the formation of ordered 2-D patterns, and APCI-MS detection proved to be an effective tool for the characterization of the complex matrix, enabling the separation and identification of nearly 60 TAGs.

1287 POSTER Palonosetron plus aprepitant and dexamethasone is a highly effective combination to prevent chemotherapy-induced nausea & vomiting after emetogenic chemotherapy

Methods based on high-performance liquid chromatography (HPLC) with atmospheric-pressure chemical ionization (APCI) mass spectrometric (MS) detection using either single (MS) or triple (MS/MS) quadrupole mass spectrometric detection for the determination of (2R)-[1(R)-(3,5-bis-trifluoromethylphenyl)ethoxy]-3(S)-(4-fluoro-phenyl)morpholin-4-ylmethyl]-5-oxo-4,5-dihydro-[1,2,4]triazol)methyl morpholine (Aprepitant, Fig. 1) in human plasma has been developed. Aprepitant (I) and internal standard (II, Fig. 1) were isolated from the plasma matrix buffered to pH 9.8 using a liquid–liquid extraction with methyl-t-butyl ether (MTBE). The analytes were separated on a Keystone Scientific’s Javelin BDS C-8 2mm×4.6 mm 3 μm guard column coupled to BDS C-8 50mm×4.6 mm 3 μm analytical column, utilizing a mobile phase of 50% acetonitrile and 50% water containing 0.1% formic acid and 10 mM ammonium acetate delivered at a flow rate of 1 ml/min. The single quadrupole instrument was operated in a single ion monitoring (SIM) mode analyzing the protonated molecules of Aprepitant and II at m/z 535 and 503, respectively. The triple quadrupole mass spectrometer was operated in multiple reaction monitoring mode (MRM) monitoring the precursor→product ion combinations of m/z 535→277 and 503→259 for Aprepitant and II, respectively. The linear calibration range for both single and triple quadrupole detectors was from 10 to 5000 ng/ml of plasma with coefficients of variation less than 8% at all concentrations. Both single and triple quadrupole instruments yielded similar precision and accuracy results. Matrix effect experiments performed on both instruments demonstrated the absence of any significant change in ionization of the analytes when comparing neat standards to analytes in the presence of plasma matrix. Both instruments were used successfully to support numerous clinical trials of Aprepitant.

Determination of a novel substance P inhibitor in human plasma by high-performance liquid chromatography with atmospheric pressure chemical ionization mass spectrometric detection using single and triple quadrupole detectors

Methods based on high-performance liquid chromatography (HPLC) with atmospheric-pressure chemical ionization (APCI) mass spectrometric (MS) detection using either single (MS) or triple (MS/MS) quadrupole mass spectrometric detection for the determination of (2 R)-[1( R)-(3,5-bis-trifluoromethylphenyl)ethoxy]-3( S)-(4-fluoro-phenyl)morpholin-4-ylmethyl]-5-oxo-4,5-dihydro-[1,2,4]triazol)methyl morpholine (Aprepitant, Fig. 1) in human plasma has been developed. Aprepitant ( I) and internal standard ( II, Fig. 1) were isolated from the plasma matrix buffered to pH 9.8 using a liquid–liquid extraction with methyl- t-butyl ether (MTBE). The analytes were separated on a Keystone Scientific’s Javelin BDS C-8 2 mm×4.6 mm 3 μm guard column coupled to BDS C-8 50 mm×4.6 mm 3 μm analytical column, utilizing a mobile phase of 50% acetonitrile and 50% water containing 0.1% formic acid and 10 mM ammonium acetate delivered at a flow rate of 1 ml/min. The single quadrupole instrument was operated in a single ion monitoring (SIM) mode analyzing the protonated molecules of Aprepitant and II at m/ z 535 and 503, respectively. The triple quadrupole mass spectrometer was operated in multiple reaction monitoring mode (MRM) monitoring the precursor→product ion combinations of m/ z 535→277 and 503→259 for Aprepitant and II, respectively. The linear calibration range for both single and triple quadrupole detectors was from 10 to 5000 ng/ml of plasma with coefficients of variation less than 8% at all concentrations. Both single and triple quadrupole instruments yielded similar precision and accuracy results. Matrix effect experiments performed on both instruments demonstrated the absence of any significant change in ionization of the analytes when comparing neat standards to analytes in the presence of plasma matrix. Both instruments were used successfully to support numerous clinical trials of Aprepitant.

Studies on the methyl isocyanate adducts with globin

Isocyanates such as methylisocyanate (MIC), an intermediate in the synthesis of carbamate pesticides, or diisocyanates, used in the production of plastics, are highly reactive toxic compounds that spontaneously bind to biological macromolecules. In vivo formation of stable adducts with blood protein globin offers possibilities for biomonitoring of internal exposure to various reactive species. Thus, biomonitoring of the isocyanates through determination of their specific adducts with globin is a challenge. In this study, we characterized the adducts formed in human globin upon treatment with 100-fold molar excess of MIC. The globin was subject to enzymatic hydrolysis with pronase, and the hydrolysate was analysed by high performance liquid chromatography with positive atmospheric pressure chemical ionization mass spectrometric detection (HPLC/APCI-MS). The two major MIC adducts were those with N-terminal Val and side-chain of Lys, as confirmed by comparison with the synthetic standards. About 20 other adducts were observed, and several of them were tentatively identified using their MS and MS/MS spectra. Whereas detection of the adducts with Tyr and His was expected, the adducts with Trp and Phe, and a Lys adduct containing two MIC moieties, were probably analytical artifacts resulting from the transcarbamoylation during globin hydrolysis rather than products of direct carbamoylation. The other detected products were MIC–Val–His, derived from the N-terminal dipeptide of globin β-chain, and dipeptides consisting of MIC–Lys attached to Gly, Val, Leu, Thr, and Glu. Failure to detect the corresponding non-modified dipeptides suggests that the pronase action may be hampered by the amino acid modification. MIC is known as a metabolic intermediate of the industrial solvents N, N-dimethylformamide (DMF) and N-methylformamide (MF) in humans and rats. The HPLC/APCI-MS analysis of globin from rats injected with DMF or MF, 1000 mg/kg, revealed the presence of the MIC adducts with both Val and Lys. The level of the Val adduct in globin from the DMF-dosed rats, determined using Edman degradation and GC/MS, was ca. 40 nmol/g, which is a level common in workers occupationally exposed to DMF. This suggests that also the Lys adduct in such human globin samples can be feasible to analysis and is therefore considered for further studies as a potential biomarker of exposure to DMF.

Products of the reaction between α- or γ-tocopherol and nitrogen oxides analyzed by high-performance liquid chromatography with UV-visible and atmospheric pressure chemical ionization mass spectrometric detection

The reaction products of α- or γ-tocopherol with nitric oxide in the presence of molecular oxygen were isolated and characterized. The consumption of tocopherols and the formation of the major products were monitored by high-performance liquid chromatography (HPLC) by a gradient elution method. The quantitative analysis of these compounds with UV-Vis detectors, however, was interfered by several minor products having similar UV spectra and retention times as those of the major ones. In order to establish a quantitative analytical method for the products, we investigated other detection methods, and found that atmospheric pressure chemical ionization (APCI), LC–MS was a more selective and better analytical method for these compounds.

Determination of lincomycin and tylosin residues in honey using solid-phase extraction and liquid chromatography-atmospheric pressure chemical ionization mass spectrometry

An analytical method for the determination of residues of the antibiotic drugs lincomycin and tylosin in honey was developed. The procedure employed a solid-phase extraction for the isolation of lincomycin and tylosin from diluted honey samples. The antibiotic residues were subsequently analyzed by reversed-phase HPLC with atmospheric pressure chemical ionization mass spectrometric detection. Average analyte recoveries for lincomycin and tylosin ranged from 84 to 107% in replicate sets of honey samples fortified with drug concentrations of 0.01, 0.5, and 10 μg/g. The method detection limits were determined to be 0.007 and 0.01 μg/g for lincomycin and tylosin, respectively.

LC-MS/MS determination of a farnesyl transferase inhibitor in human plasma and urine

To support clinical pharmacokinetic studies in cancer patients, sensitive and specific methods for measuring 4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-1-(3-chlorophenyl) piperazinone (I), a farnesyl transferase inhibitor (FTI), in human plasma and urine were developed and validated. The methods are based on high-performance liquid chromatography (HPLC) with atmospheric pressure chemical ionization (APCI) and tandem mass spectrometric (MS/MS) detection in the positive ion mode using a heated nebulizer interface. Drug and internal standard were isolated from plasma or basified urine using automated solid-phase extraction on cyano cartridges. The organic extracts were dried, reconstituted in aqueous acetonitrile and injected into the system. Chromatographic separation of I and internal standard ( IS) was achieved using a BDS Hypersil C8 analytical column, with a mobile phase consisting of acetonitrile:methanol:water (50:4:46) and trifluoroacetic acid (0.05%) at a flow rate of 0.6 ml/min. MS/MS detection was performed on a PE-Sciex API 300 tandem mass spectrometer operated in selected reaction monitoring mode. The parent→product ions monitored were m/ z 406→195 for analyte I and m/ z 448→195 for the internal standard. Unusual in this method is that quantitation is accomplished using a secondary product ion, m/ z 195, of drug I and IS. The assays were validated over the concentration range of 0.5–1000 ng/ml (1.2 nM to 2.5 μM, respectively) in plasma, and 2.5–500 ng/ml (6.2 nM to 1.23 μM) in urine. Accuracy was within ±10% of nominal concentration at all levels in urine, and all but the lowest standard in plasma (±14% at 0.5 ng/ml). Intraday precision (expressed as coefficients of variation, CVs) for standard replicates and interday precision for quality control (QC) samples were less than 8% at all concentrations in both matrices. Detailed descriptions of the extraction procedure and analytical methodology used in the assay of I in plasma and urine are presented. This procedure may have utility in the quantitation of other imidazole-based FTIs with cyanobenzyl substructures.