Pressure Ionization Mass Spectrometry Research Articles

Mass spectrometry: Fifth meeting of the Spanish Society of Mass Spectrometry (SEEM)

Keeping its biannual pattern, the Spanish Society of Mass Spectrometry (SEEM) celebrated its fifth meeting in the town of Malaga, capital of the Sunny Coast, from 11 to 14 April 2011. If the classic sentence “the ghosts of the past survive in the uncertainty of your future” applies in many vital situations, when it comes to organizing a scientific meeting, the success of previous meetings is a heavy load hanging around the organizer’s neck. For this particular conference, the outstanding organization and excellence of the work reported at previous meetings (Madrid 2002, Barcelona 2004, Oviedo 2006, and Castellon 2009) were additional weights to the difficult enterprise of fulfilling expectations. Luckily, the gracious advice of the Board of Directors of SEEM, the impressive work of the secretary and vicepresident of the organizing committee (Helena Tellez-Lozano and Alegria Carrasco-Pancorbo), and the excellent logistic support of Proyectos, Incentivos y Congresos were key factors in the final success of the meeting. Despite its youth (SEEM was officially established in 2000 during the International Mass Spectrometry Conference organized by Emilio Gelpi in Barcelona) and the dissemination of the mass spectrometrists community in Spain among diverse scientific societies (Society of Chromatography and Related Techniques; Spanish Society of Analytical Chemistry, Society of Applied Spectroscopy, Society of Proteomics, and the Royal Society of Chemistry), the conference has grown significantly in delegates (from academia, public/private laboratories, and instrumentation companies) and currently has a national reputation as the meeting point of mass spectrometry in Spain to foster discussions, exchange experience, and improve knowledge with colleagues that share a common interest in the crazy idea of chasing ions in the gas phase. In this direction, most important were the efforts that SEEM made in helping young researchers to attend the meeting at zero cost in the belief that the mutual interaction of seniors and juniors is the only way to provide the relaxing and potential-free surface where the spark of science begins. The conference was attended by more than 150 scientists, including about 50 young researchers (Ph.D. students and postdoctoral researchers). The scientific program was opened on the evening of April 11th with a single plenary lecture given by Professor Maria Teresa Galceran (Universidad Autonoma de Barcelona, Spain), one of the most relevant scientists in Spain, on the use of mass spectrometry in analytical chemistry. Her talk, entitled “LC–MS tools for environmental and food analysis” provided a beautiful view (with many surprising examples) of the power of LC–MS in the complex context of food and environmental analysis. After her captivating talk, the attendees had the chance to enjoy an open-air mixing party under a beautiful and cloudless sky and a warm temperature. The conference continued for two and a half days with three more exceptional plenary speakers. Akos Vertes (George Washington University, USA) shared with us the exciting world of mass spectrometry of cells and tissues by the combination of tuneable mid-infrared lasers for spatially localized sampling followed by atmospheric-pressure ionization mass spectrometry. Olev Mayboroda (Leiden University Medical Centre, the Netherlands) with an intriguing title for his talk (Metabollomics: the art of possible), took J. M. Vadillo Department of Analytical Chemistry, University of Malaga, 29071 Malaga, Spain

Natural dissolved organic matter affects electrospray ionization during analysis of emerging contaminants by mass spectrometry

Dissolved organic matter (DOM), present in many forms in water, can interfere with analysis of organic contaminants by atmospheric pressure ionization–mass spectrometry. A quantitative analysis of this interference, or matrix effect, on organic contaminant target analyte measurements was carried out using un-fractionated and fractionated dissolved natural organic matter from the Suwannee River, GA (SROM), a standard reference material, that was directly infused into the tandem mass spectrometer during multiple reaction monitoring (MRM) of a suite of endocrine disrupting compounds–pharmaceuticals and personal care products (EDC/PPCPs). Most target analytes suffered signal suppression in the presence of both fractionated and un-fractionated SROM, however greater interferences were measured with fractionated relative to bulk SROM. This finding is consistent with the view of organic matter as a supramolecular association of low molecular mass components having separate charged and structural features revealed only after dissociation.

Reactions of OH Radicals with C6–C10 Cycloalkanes in the Presence of NO: Isomerization of C7–C10 Cycloalkoxy Radicals

Rate constants have been measured for the reactions of OH radicals with a series of C(6)-C(10) cycloalkanes and cycloketones at 298 ± 2 K, by a relative rate technique. The measured rate constants (in units of 10(-12) cm(3) molecule(-1) s(-1)) were cycloheptane, 11.0 ± 0.4; cyclooctane, 13.5 ± 0.4; cyclodecane, 15.9 ± 0.5; cyclohexanone, 5.35 ± 0.10; cycloheptanone, 9.57 ± 0.41; cyclooctanone, 15.4 ± 0.7; and cyclodecanone, 20.4 ± 0.8, where the indicated errors are two least-squares standard deviations and do not include uncertainties in the rate constant for the reference compound n-octane. Formation yields of cycloheptanone from cycloheptane (4.2 ± 0.4%), cyclooctanone from cyclooctane (0.85 ± 0.2%), and cyclodecanone from cyclodecane (4.9 ± 0.5%) were also determined by gas chromatography, where the molar yields are in parentheses. Analyses of products by direct air sampling atmospheric pressure ionization mass spectrometry and by combined gas chromatography-mass spectrometry showed, in addition to the cycloketones, the presence of cycloalkyl nitrates, cyclic hydroxyketones, hydroxydicarbonyls, hydroxycarbonyl nitrates, and products attributed to carbonyl nitrates and/or cyclic hydroxynitrates. The observed formation of cyclic hydroxyketones from the cycloheptane, cyclooctane and cyclodecane reactions, with estimated molar yields of 46%, 28%, and 15%, respectively, indicates the occurrence of cycloalkoxy radical isomerization. Potential reaction mechanisms are presented, and rate constants for the various alkoxy radical reactions are derived.

Degradation Mechanism of Aqueous Sulfamerazine by AOPs of O<sub>3</sub> and UV/TiO<sub>2</sub>

Advanced Oxidation Processes (AOPs) is a promising treatment technology for eliminating trace micropollutants, in the treatment of wastewaters containing sulfamerazine (one of pharmaceuticals) using O3 and UV/TiO2 process, respectively. The degradation was studied by monitoring the intermediates employing high performance liquid chromatography (HPLC) separation coupled with an atmospheric pressure ionization mass spectrometry (API-MS) system operated under selected ion monitoring (SIM). The results indicate that the original sulfamerazine almost was degraded within 90 min under the concentration of ozone 3 mg/L at different pH runs. The ozonation of sulfamerazine demonstrated the best degradation efficiency for runs at pH 8 than for runs at pH 6 and pH 11, respectively, under the concentration of ozone 1 or 3 mg/L. The original sulfamerazine was completely degraded within irradiation time of 5 hr at pH 6 runs in the concentration of O2-sparged 30 mg/L during the photocatalytic process. The rate constants are 0.086, 0.08, 0.04, and 0.027 hr-1 at the concentration of sulfamerazine 14.22, 21.33, 35.55, and 42.66 μM, respectively. Two intermediates were observed during the photocatalytic degradation of sulfamerazine.

Inter‐individual variability in aroma release during sweet mint consumption

Inter-individual variations of in vivo aroma release kinetics have been observed widely in the literature. However, the corresponding causes are yet to be clearly identified. For this purpose, 68 subjects in whom salivary flow rates (at rest and Parafilm™-stimulated) had been determined were recruited for the study. The release of menthone was measured using atmospheric pressure ionisation–mass spectrometry during the consumption of a sweet mint tablet. The subjects complied with an imposed protocol of oral movements. Inter-individual variability was investigated through a qualitative analysis of the oral movements inducing menthone release, and through quantitative analysis. Swallowing events were the main contributors to menthone release. Tongue and jaw movements did not induce menthone release in all the subjects, thus explaining inter-individual differences in menthone release curve profiles. Inter-individual differences in term of the quantity of menthone released partly arose from the percentage of sweet mint tablet degradation. The greater the degree of degradation, the more menthone was released. Although protein concentrations in the saliva gave a first indication of differences in mint tablet degradation between subjects, other factors such as the content of specific proteins, and particularly enzymes, still need to be explored. Copyright © 2011 John Wiley & Sons, Ltd.

Inter‐individual variability in aroma release during sweet mint consumption

ABSTRACTInter‐individual variations of in vivo aroma release kinetics have been observed widely in the literature. However, the corresponding causes are yet to be clearly identified. For this purpose, 68 subjects in whom salivary flow rates (at rest and Parafilm™‐stimulated) had been determined were recruited for the study. The release of menthone was measured using atmospheric pressure ionisation–mass spectrometry during the consumption of a sweet mint tablet. The subjects complied with an imposed protocol of oral movements. Inter‐individual variability was investigated through a qualitative analysis of the oral movements inducing menthone release, and through quantitative analysis. Swallowing events were the main contributors to menthone release. Tongue and jaw movements did not induce menthone release in all the subjects, thus explaining inter‐individual differences in menthone release curve profiles. Inter‐individual differences in term of the quantity of menthone released partly arose from the percentage of sweet mint tablet degradation. The greater the degree of degradation, the more menthone was released. Although protein concentrations in the saliva gave a first indication of differences in mint tablet degradation between subjects, other factors such as the content of specific proteins, and particularly enzymes, still need to be explored. Copyright © 2011 John Wiley & Sons, Ltd.

Atmospheric Chemistry of Dichlorvos

Dichlorvos [2,2-dichlorovinyl dimethyl phosphate, (CH(3)O)(2)P(O)OCH═CCl(2)] is a relatively volatile in-use insecticide. Rate constants for its reaction with OH radicals have been measured over the temperature range 296-348 K and atmospheric pressure of air using a relative rate method. The rate expression obtained was 3.53 × 10(-13) e((1367±239)/T) cm(3) molecule(-1) s(-1), with a 298 K rate constant of (3.5 ± 0.7) × 10(-11) cm(3) molecule(-1) s(-1), where the error in the 298 K rate constant is the estimated overall uncertainty. In addition, rate constants for the reactions of NO(3) radicals and O(3) with dichlorvos, of (2.5 ± 0.5) × 10(-13) cm(3) molecule(-1) s(-1) and (1.7 ± 1.0) × 10(-19) cm(3) molecule(-1) s(-1), respectively, were measured at 296 ± 2 K. Products of the OH and NO(3) radical-initiated reactions were investigated using in situ atmospheric pressure ionization mass spectrometry (API-MS) and (OH radical reaction only) in situ Fourier transform infrared (FT-IR) spectroscopy. For the OH radical reaction, the major initial products were CO, phosgene [C(O)Cl(2)] and dimethyl phosphate [(CH(3)O)(2)P(O)OH], with equal (to within ±10%) formation yields of CO and C(O)Cl(2). The API-MS analyses were consistent with formation of (CH(3)O)(2)P(O)OH from both the OH and NO(3) radical-initiated reactions. In the atmosphere, the dominant chemical loss processes for dichlorvos will be daytime reaction with OH radicals and nighttime reaction with NO(3) radicals, with an estimated lifetime of a few hours.

Kinetics of the Reactions of OH Radicals with 2- and 3-Methylfuran, 2,3- and 2,5-Dimethylfuran, andE- andZ-3-Hexene-2,5-dione, and Products of OH + 2,5-Dimethylfuran

Furan and alkylfurans are present in the atmosphere from direct emissions and in situ formation from other volatile organic compounds. The OH radical-initiated reactions of furan and alkylfurans have been proposed as relatively clean in situ sources of unsaturated 1,4-dicarbonyls, some of which are otherwise not readily available. Using a relative rate method, rate constants at 296 ± 2 K for the gas-phase reactions of OH radicals with 2- and 3-methylfuran, 2,3- and 2,5-dimethylfuran, and Z- and E-3-hexene-2,5-dione have been measured, of (in units of 10(-11) cm(3) molecule(-1) s(-1)): 2-methylfuran, 7.31 ± 0.35; 3-methylfuran, 8.73 ± 0.18; 2,3-dimethylfuran, 12.6 ± 0.4; 2,5-dimethylfuran, 12.5 ± 0.4; Z-3-hexene-2,5-dione, 5.90 ± 0.57; and E-3-hexene-2,5-dione, 4.14 ± 0.02. Products of the OH radical-initiated reaction of 2,5-dimethylfuran were investigated, with 3-hexene-2,5-dione being formed with molar yields of 24 ± 3% in the presence of NO and 34 ± 3% in the absence of NO. Direct air sampling atmospheric pressure ionization mass spectrometry showed the formation of additional products of molecular weight 114, attributed to CH(3)C(O)CH ═ CHC(O)OH and/or 5-hydroxy-5-methyl-2-furanone, and 128, attributed to CH(3)C(O)OC(CH(3)) = CHCHO.

Nitrate Ion Photolysis in Thin Water Films in the Presence of Bromide Ions

Nitrate ions commonly coexist with halide ions in aged sea salt particles, as well as in the Arctic snowpack, where NO(3)(-) photochemistry is believed to be an important source of NO(y) (NO + NO(2) + HONO + ...). The effects of bromide ions on nitrate ion photochemistry were investigated at 298 ± 2 K in air using 311 nm photolysis lamps. Reactions were carried out using NaBr/NaNO(3) and KBr/KNO(3) deposited on the walls of a Teflon chamber. Gas phase halogen products and NO(2) were measured as a function of photolysis time using long path FTIR, NO(y) chemiluminescence and atmospheric pressure ionization mass spectrometry (API-MS). Irradiated NaBr/NaNO(3) mixtures show an enhancement in the rates of production of NO(2) and Br(2) as the bromide mole fraction (χ(NaBr)) increased. However, this was not the case for KBr/KNO(3) mixtures where the rates of production of NO(2) and Br(2) remained constant over all values of χ(KBr). Molecular dynamics (MD) simulations show that the presence of bromide in the NaBr solutions pulls sodium toward the solution surface, which in turn attracts nitrate to the interfacial region, allowing for more efficient escape of NO(2) than in the absence of halides. However, in the case of KBr/KNO(3), bromide ions do not appreciably affect the distribution of nitrate ions at the interface. Clustering of Br(-) with NO(3)(-) and H(2)O predicted by MD simulations for sodium salts may facilitate a direct intermolecular reaction, which could also contribute to higher rates of NO(2) production. Enhanced photochemistry in the presence of halide ions may be important for oxides of nitrogen production in field studies such as in polar snowpacks where the use of quantum yields from laboratory studies in the absence of halide ions would lead to a significant underestimate of the photolysis rates of nitrate ions.

Photocatalytic Degradation Mechanism and Kinetics of Caffeine in Aqueous Suspension of Nano-TiO<sub>2</sub>

This study investigated TiO2 photocatalytic degradation of caffeine, a stimulating drug, in aqueous suspensions of titanium dioxide under a variety of conditions. Pure TiO2 powders were prepared using a modified homogeneous-precipitation process at low temperature (HPPLT) method. The degradation was studied by monitoring the intermediates employing high performance liquid chromatography (HPLC) separation coupled to an atmospheric pressure ionization mass spectrometry (API-MS) system operated under selected ion monitoring (SIM). These results indicate the original concentration of caffeine almost completely degraded within 360 min, and a degradation ratio of more than 50 % appearing within 120 min of irradiation in a pH range of 3—10. The reaction rates for the decomposition of caffeine in water are higher for runs at pH 3 (k = 0.013 min-1) and pH 11 (k = 0.012 min-1). The proposed conversion mechanism of caffeine was used. The caffeine was first oxidized to become dimethyl parabanic acid and further degraded to di(hydroxymethyl) parabanic acid. This study also detected the product from N-demthylation, theophyline.

Degradation Characteristics of Sulfamethoxypyridazine in Water by Ozonation and Photocatalysis

Pharmaceuticals and personal care products (PPCPs) have emerged as a major class of contaminants, given their widespread usage and known biological effects. Sulphonamides are synthetic antibacterial agents widely used in veterinary practice for the treatment of infections and to promote the growth of food-producing animals. Traditional sewage treatment procedures are unable to get rid of these compounds effectively. Advanced oxidation processes (AOPs) are a promising technology for treating wastewaters containing sulfamethoxypyridazine pharmaceuticals via O3 and UV/TiO2 process. This study performs batch experiments to determine the effects of operating parameters on the degradation efficiencies of sulfamethoxypyridazine. The degradation was studied by monitoring the intermediates employing high performance liquid chromatography (HPLC) separation coupled to an atmospheric pressure ionization mass spectrometry (API-MS) system operating under selected ion monitoring (SIM). Results show that complete removal of all sulfamethoxypyridazine was achieved within 80min of ozonation at the concentration of O3 (3ppm) at different pH runs. The ozonation of sulfamethoxypyridazine demonstrated the best degradation efficiency for runs at pH 8, followed by runs at pH 6 and pH 11. The ozonation imposed sulfamethoxypyridazine with a time dependence that appeared to follow pseudo first-order kinetics. The original concentration of sulfamethoxypyridazine almost completely degraded within 7 hr in UV/TiO2 at pH 6 runs. The reaction rates for the decomposition of sulfamethoxypyridazine in water are higher at pH 6 run than for runs at pH 3 and pH 11. Three organic intermediates appeared during the photocatalytic degradation of sulfamethoxypyridazine.

On the Presence and Role of Polar Lipids in Meibum

On the Presence and Role of Polar Lipids in Meibum

IDENTIFICATION OF PHENOLIC AND CAROTENOID COMPOUNDS IN CARICA PAPAYA L. 'MARADOL' USING LIQUID CHROMATOGRAPHY - MASS SPECTROMETRY

Plant phenolic and carotenoid compounds are known for their beneficial effects on human health, and they are present in a great variety of fruits and vegetables. The profile of bioactive compounds in papaya fruit has not been completely elucidated and research has been focused on characterization of mature fruit flesh composition and proteolitic enzymes with industrial applications. The objective of this work was to identify potential bioactive compounds previously related to health improvement, in papaya peel and flesh tissues during storage at 25°C. Samples of peel and flesh tissue of C. papaya fruits were submitted to solvent extraction and hydrolysis in order to identify free and conjugated phenolics by liquid chromatography/diode array detector coupled to electro spray ionization mass spectrometry (LC/DAD-MS-ESI). Caffeic acid, protocatechuic acid-hexoside, sinapic acid, quercetin-3-O-rutinoside, ferulic acid, myricetin, quercetin, isorhamnetin, kaempferol, caffeoylhexose-deoxyhexose, caffeoylhexoside and gallic acid-deoxyhexoside phenolics were found in peel extracts while caffeic acid, protocatechuic acid and gallic acid hexosides were present in the flesh. Carotenoids were identified in the flesh by LC/DAD coupled to atmospheric pressure ionization mass spectrometry (LC/DAD-MS-APCI). Lycopene, β-criptoxhantin and β-carotene were the most abundant carotenoids in that order. No significant differences were observed in phenolic profile during storage; however, lycopene and β-criptoxhantin levels tend to increase in storage. Identified phenolic and carotenoid compounds have proved to act as potent antioxidants in biological systems, and some are presumed to act as preventative anticarcinogens agents in vitro and in vivo. The presence of these compounds could explain the health benefits attributed to this fruit, and opens future studies towards mode of action elucidation in biological systems.

An overview of matrix effects in liquid chromatography–mass spectrometry

Matrix-dependent signal suppression or enhancement represents a major drawback in quantitative analysis with liquid chromatography coupled to atmospheric pressure ionization mass spectrometry (LC-API-MS). Because matrix effects (ME) might exert a detrimental impact on important method parameters (limit of detection, limit of quantification, linearity, accuracy, and precision), they have to be tested and evaluated during validation procedure. This review gives a detailed description on when these phenomena might be expected, and how they can be evaluated. The major sources of ME are discussed and illustrated with examples from bioanalytical, pharmaceutical, environmental, and food analysis. Because there is no universal solution for ME, the main strategies to overcome these phenomena are described in detail. Special emphasis is devoted to the sample-preparation procedures as well as to the recent improvements on chromatographic and mass spectrometric conditions. An overview of the main calibration techniques to compensate for ME is also presented. All these solutions can be used alone or in combination to retrieve the performance of the LC-MS for a particular matrix-analyte combination.

Pitfalls Associated with the Use of Liquid Chromatography–Tandem Mass Spectrometry in the Clinical Laboratory

Novel mass spectrometric techniques such as atmospheric pressure ionization and tandem mass spectrometry have substantially extended the spectrum of clinical chemistry methods during the past decade. In particular, liquid chromatography tandem-mass spectrometry (LC-MS/MS) has become a standard tool in research laboratories as well as in many clinical laboratories. Although LC-MS/MS has features that suggest it has a very high analytical accuracy, potential sources of inaccuracy have recently been identified. The sources of inaccuracy in LC-MS/MS methods used in the routine quantification of small molecules are described and discussed. Inaccuracy of LC-MS/MS methods can be related to the process of ionization through the insource transformation of conjugate metabolites or target analytes and may also be attributable to ionization matrix effects that have a differential impact on target analytes and internal-standard compounds. Inaccuracy can also be associated with the process of ion selection, which mainly occurs when compounds from the sample matrix share mass transitions with a target analyte. In individual assays, most potential sources of inaccuracy can be controlled by sufficient LC separation-based sample workup before MS analysis. LC-MS/MS methods should undergo rigorous and systematic validation before introduction into patient care.

MATRIX EFFECTS IN LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY

Despite their enormous utility and diffusion, atmospheric pressure ionization mass spectrometry techniques are subjected to relevant drawbacks called matrix effects (ME). These effects could be summarized in matrix-dependent signal suppression or enhancement that could lead to erroneous quantitative results. The most important method parameters as well as linearity, precision, and accuracy could be modified due to interfering compounds present in the matrix. No validation methods could be accepted without a thorough evaluation of ME and possible strategies to minimize or to correct their influence should be addressed. In this article, we investigate mechanisms that lead to ME and discuss calibration techniques and other strategies to limit these phenomena. Significant examples from different fields of application are discussed as well. Sample preparation procedures, together with instrumental improvements and alternative calibration techniques used by many authors, are reported.

Kinetics and Products of the Reactions of OH Radicals with 4,4-Dimethyl-1-pentene and 3,3-Dimethylbutanal at 296 ± 2 K

Using a relative rate method, rate constants have been measured for the reactions of OH radicals with 4,4-dimethyl-1-pentene [(CH(3))(3)CCH(2)CH=CH(2)] and its major reaction product, 3,3-dimethylbutanal [(CH(3))(3)CCH(2)CHO], at 296 +/- 2 K and atmospheric pressure of air. The rate constants obtained were 2.41 x 10(-11) and 2.73 x 10(-11) cm(3) molecule(-1) s(-1), respectively, with estimated uncertainties of +/-10%. The products identified and quantified by gas chromatography with mass spectrometry and/or flame ionization detection from the 4,4-dimethyl-1-pentene reaction were acrolein [CH(2)=CHCHO], 3,3-dimethylbutanal, and a molecular weight 112 carbonyl attributed to 4,4-dimethyl-2-pentenal [(CH(3))(3)CCH=CHCHO], with formation yields of 2.7 +/- 0.5%, 59 +/- 6%, and 3.4 +/- 0.6%, respectively. Using direct air sampling atmospheric pressure ionization mass spectrometry, additional products of molecular weight 146, 177, and 193 were observed, and on the basis of expected reaction schemes these are attributed to the dihydroxycarbonyl HOCH(2)C(CH(3))(2)CH(2)C(O)CH(2)OH, the hydroxynitrates (CH(3))(3)CCH(2)CH(OH)CH(2)ONO(2) and/or (CH(3))(3)CCH(2)CH(ONO(2))CH(2)OH, and the dihydroxynitrate O(2)NOCH(2)C(CH(3))(2)CH(2)CH(OH)CH(2)OH, respectively. The hydroxynitrates were also tentatively identified by gas chromatography, with a summed yield of approximately 15%. Acrolein and 4,4-dimethyl-2-pentenal arise from H-atom abstraction from the three equivalent CH(3) groups and the 3-position CH(2) group, and the sum of their formation yields (6.1 +/- 0.8%) is expected to be very close to the fraction of the overall reaction proceeding by H-atom abstraction.

An experimental and computational study on the dissociation behavior of hydroxypyridine N‐oxides in atmospheric pressure ionization mass spectrometry

A tandem mass spectrometric study of protonated isomeric hydroxypyridine N-oxides was carried out with a hybrid quadrupole/time-of-flight mass spectrometer coupled with different atmospheric pressure ionization sources. The behavior observed in the collision-induced dissociation (CID) mass spectra of the parent cations, was similar irrespective of the source employed. However, there were intrinsic differences in the intensities of the two fragments observed for each isomer. The major fragment because of elimination of a hydroxyl radical, dominated the CID spectra (in contrast with weaker water loss) at different energy thresholds. Therefore, it was possible to differentiate both isomers at collision energies above 13 eV by comparing the ratio of intensities of the major fragment relative to the precursor cation. In addition, quantum chemical calculations at the B3LYP/6-31 + + G(d,p) level of theory were performed for the protonated isomers of hydroxypyridine N-oxide and their radical cation products in order to gain insight into the major routes of dissociation. The results suggest that dissociation from the lowest triplet excited state of the protonated species would provide a reasonable rationalization for the difference in behavior of both isomers.

Atmospheric Chemistry of Isopropyl Methyl Methylphosphonate and Dimethyl N,N-Dimethylphosphoroamidate

Rate constants for the reactions of OH radicals with isopropyl methyl methylphosphonate [(CH(3))(2)CHOP(O)(CH(3))OCH(3); IMMP] and dimethyl N,N-dimethylphosphoroamidate [(CH(3)O)(2)P(O)N(CH(3))(2); DMDMPA] have been measured over the temperature range 283-350 K and atmospheric pressure of air using a relative rate method. The rate expressions obtained were 2.72 x 10(-13) e((1642+/-144)/T) cm(3) molecule(-1) s(-1) (6.72 x 10(-11) cm(3) molecule(-1) s(-1) at 298 K) for OH + IMMP and 6.05 x 10(-13) e((1185+/-144)/T) cm(3) molecule(-1) s(-1) (3.23 x 10(-11) cm(3) molecule(-1) s(-1) at 298 K) for OH + DMDMPA. In addition, rate constants for the reactions of NO(3) radicals and O(3) with IMMP were measured at 296 +/- 2 K, of (4.8 +/- 2.1) x 10(-16) and <7 x 10(-20) cm(3) molecule(-1) s(-1), respectively. Products of the OH radical-initiated reactions were investigated using gas chromatography, in situ atmospheric pressure ionization mass spectrometry (API-MS), and in situ Fourier transform infrared (FT-IR) spectroscopy. For the OH + IMMP reaction, the major initial products appear to be CH(3)OP(O)(CH(3))OC(O)CH(3) + (*)CH(3), with subsequent reactions of the methyl radical in the presence of NO(x) leading to HCHO, CH(3)ONO, and CH(3)ONO(2). For the OH + DMDMPA reaction, (CH(3)O)(2)P(O)N(CH(3))CHO was observed as a significant product. Possible reaction mechanisms are discussed.

In-vitro metabolism of isotetrandrine, a bisbenzylisoquinoline alkaloid, in rat hepatic S9 fraction by high-performance liquid chromatography-atmospheric pressure ionization mass spectrometry.

The objective of this study was to investigate the in-vitro metabolism of isotetrandrine, a bisbenzylisoquinoline alkaloid, using rat hepatic S9 fraction and to profile and identify its metabolites using high-performance liquid chromatography-atmospheric pressure ionization mass spectrometry (HPLC-MS) and tandem mass spectrometry (MS/MS). Isotetrandrine was incubated at a concentration of 100 microg mL(-1) with male rat hepatic S9 fraction in the presence of an NADPH generating system (Tris buffer, pH 7.4, 37 degrees C). Samples were removed at 60 min after reaction initiation. Unchanged isotetrandrine (approximately 63% of the sample) and four metabolites were profiled, characterized and tentatively identified using solvent extraction, methyl derivatization, and HPLC-MS and MS/MS techniques. Isotetrandrine metabolites were mainly formed via two main pathways, N-demethylation and isoquinoline ring oxidation. The first pathway produced a major metabolite, N-desmethyl isotetrandrine (approximately 16% of the sample). The second pathway produced three minor oxidized metabolites, hydroxy-isotetrandrine (approximately 6% of the sample), oxo-isotetrandrine (approximately 7% of the sample), and oxohydroxy-isotetrandrine (approximately 7% of the sample). Diazomethane treatment of these metabolites did not produce any methyl derivatives and therefore the hydroxylated sites of the metabolites were tentatively assigned at the heterocyclic moieties of the isoquinoline rings. In conclusion, isotetrandrine is substantially metabolized in this in-vitro rat hepatic system.