APCI Source Research Articles

Miniaturized flexible micro-tube plasma ionization source for the effective ionization of non-easily ionizable pesticides in food with liquid chromatography/mass spectrometry

In this article, we have studied the potential of flexible microtube plasma (FμTP) as ionization source for the liquid chromatography high-resolution mass spectrometry detection of non-easily ionizable pesticides (viz. nonpolar and non-ionizable by acid/basic moieties). Phthalimide-related compounds such as dicofol, dinocap, o-phenylphenol, captan, captafol, folpet and their metabolites were studied. Dielectric barrier discharge ionization (DBDI) was examined using two electrode configurations, including the miniaturized one based on a single high-voltage (HV) electrode and a virtual ground electrode configuration (FμTP), and also the two-ring electrode DBDI configuration. Different ionization pathways were observed to ionize these challenging, non-easily ionizable nonpolar compounds, involving nucleophilic substitutions and proton abstraction, with subtle differences in the spectra obtained compared with APCI. An average sensitivity increase of 5-fold was attained compared with the standard APCI source. In addition, more tolerance with matrix effects was observed in both DBDI sources. The importance of the data reported is not just limited to the sensitivity enhancement compared to APCI, but, more notably, to the ability to effectively ionize nonpolar, late-eluting (in reverse-phase chromatography) non-ionizable compounds. Besides o-phenylphenol ([M − H]-), all the parent species were efficiently ionized through different mechanisms involving bond cleavages through the effect of plasma reagent species or its combination with thermal degradation and subsequent ionization. This tool can be used to figure out overlooked nonpolar compounds in different environmental samples of societal interest through non-target screening (NTS) strategies.

Simultaneous detection of furfural, 5-methylfurfural and 5-hydroxymethylfurfural in tsamba, roasted highland barley flour, by UPLC–MS/MS

Tsamba, roasted highland barley flour, is the traditional staple food of Tibet Autonomous Region. In this work, a sensitive and fast method was developed and validated for the simultaneous analysis of furfural, 5-methylfurfural and 5-hydroxymethylfurfural in tsamba by UPLC–MS/MS with APCI source. The extracted tsamba samples were purified by optimized QuEChERS purification sorbents. The target compounds were detected by tandem mass spectrometry in MRM mode, and quantified by using internal standards of D4-furfural and 13C6-5-(hydroxymethyl)furfural. Good linearities were obtained (r > 0.999) in the range of 2–100 μg/L for furfural, 1–50 μg/L for 5-methylfurfural and 10–500 μg/L for 5-(hydroxymethyl)furfural. The mean recoveries ranged from 89.5% to 106% for all the analytes, with coefficients of variation less than 10%. Low limits of quantification of the method were obtained. Finally, the method was successfully applied to the analysis of tsamba samples from Lhasa (Tibet, China). The results showed that furanic compounds were detected in all tsamba samples. The health risk assessment of furfural indicated potential risk for human consumption of tsamba for rural residents in Lhasa, and a per capita consumption of tsamba less than 180 g/person/day was recommended.

First Novel Workflow for Semiquantification of Emerging Contaminants in Environmental Samples Analyzed by Gas Chromatography-Atmospheric Pressure Chemical Ionization-Quadrupole Time of Flight-Mass Spectrometry.

The ionization efficiency of emerging contaminants was modeled for the first time in gas chromatography-high-resolution mass spectrometry (GC-HRMS) which is coupled to an atmospheric pressure chemical ionization source (APCI). The recent chemical space has been expanded in environmental samples such as soil, indoor dust, and sediments thanks to recent use of high-resolution mass spectrometric techniques; however, many of these chemicals have remained unquantified. Chemical exposure in dust can pose potential risk to human health, and semiquantitative analysis is potentially of need to semiquantify these newly identified substances and assist with their risk assessment and environmental fate. In this study, a rigorously tested semiquantification workflow was proposed based on GC-APCI-HRMS ionization efficiency measurements of 78 emerging contaminants. The mechanism of ionization of compounds in the APCI source was discussed via a simple connectivity index and topological structure. The quantitative structure–property relationship (QSPR)-based model was also built to predict the APCI ionization efficiencies of unknowns and later use it for their quantification analyses. The proposed semiquantification method could be transferred into the household indoor dust sample matrix, and it could include the effect of recovery and matrix in the predictions of actual concentrations of analytes. A suspect compound, which falls inside the application domain of the tool, can be semiquantified by an online web application, free of access at http://trams.chem.uoa.gr/semiquantification/.

Structural Characterization of Unusual Fatty Acid Methyl Esters with Double and Triple Bonds Using HPLC/APCI-MS2 with Acetonitrile In-Source Derivatization.

Double and triple bonds have significant effects on the biological activities of lipids. Determining multiple bond positions in their molecules by mass spectrometry usually requires chemical derivatization. This work presents an HPLC/MS method for pinpointing the double and triple bonds in fatty acids. Fatty acid methyl esters were separated by reversed-phase HPLC with an acetonitrile mobile phase. In the APCI source, acetonitrile formed reactive species, which added to double and triple bonds to form [M + C3H5N]+• ions. Their collisional activation in an ion trap provided fragments helpful in localizing the multiple bond positions. This approach was applied to fatty acids with isolated, cumulated, and conjugated double bonds and triple bonds. The fatty acids were isolated from the fat body of early-nesting bumblebee Bombus pratorum and seeds or seed oils of Punicum granatum, Marrubium vulgare, and Santalum album. Using the method, the presence of the known fatty acids was confirmed, and new ones were discovered.

Identification of new, very long-chain polyunsaturated fatty acids in fish by gas chromatography coupled to quadrupole/time-of-flight mass spectrometry with atmospheric pressure chemical ionization.

The characterization of very long-chain (>C24) polyunsaturated fatty acids (VLC-PUFAs), which are essential in the vision, neural function, and reproduction of vertebrates, is challenging because of the lack of reference standards and their very low concentrations in certain lipid classes. In this research, we have developed a new methodology for VLC-PUFA identification based on gas chromatography coupled to quadrupole/time-of-flight mass spectrometry with an atmospheric pressure chemical ionization source (GC-APCI-QTOF MS). The mass accuracy attainable with the innovative QTOF instrument, together with the soft ionization of the APCI source, provides valuable information on the intact molecule, traditionally lost with electron ionization sources due to the extensive fragmentation suffered. We have identified, for the first time, VLC-PUFAs with chains up to 44 carbons in eyes, brain, and gonads of gilthead sea bream, a commercially important fish in the Mediterranean. The added value of ion mobility-mass spectrometry (IMS), recently developed in combination with GC-QTOF MS, and the contribution of the collisional cross section (CCS) parameter in the characterization of novel VLC-PUFAs (for which reference standards are not available) have been also evaluated. The methodology developed has allowed assessing qualitative differences between farmed and wild fish, and opens new perspectives in a still scarcely known field of research.

Identification and characterization of impurities in an insecticide, bifenthrin technical.

The HPLC-DAD and GC/MS methods were successfully used for the identification and characterization of the impurities in an agrochemical insecticide, bifenthrin technical. Three impurities ranging from 0.175%-0.541% were detected by the HPLC-DAD method. The LC/MS technique with ESI or APCI source failed to detect the impurities detected by HPLC-DAD, due to lack of ionization in ESI or APCI. The three impurities were enriched by prep-HPLC, and then their structures were elucidated based on the GC/EIMS and CIMS data. The EI mass spectra of bifenthrin and its impurities displayed molecular ion and provided structure indicative fragment ions; the CIMS data further confirmed their molecular weight. The identity of the impurity 1 was further confirmed by the synthesis of the authentic sample followed by NMR and GC/MS data.

LC-MS/MS Method for the Quantitative Determination of Tanespimycin and its Active Metabolite in Human Plasma: Method Validation and Overcoming an Insidious APCI Source Phenomenon

LC-MS/MS Method for the Quantitative Determination of Tanespimycin and its Active Metabolite in Human Plasma: Method Validation and Overcoming an Insidious APCI Source Phenomenon

Characterization of volatile metabolites formed by molds on barley by mass and ion mobility spectrometry.

The contamination of barley by molds on the field or in storage leads to the spoilage of grain and the production of mycotoxins, which causes major economic losses in malting facilities and breweries. Therefore, on-site detection of hidden fungus contaminations in grain storages based on the detection of volatile marker compounds is of high interest. In this work, the volatile metabolites of 10 different fungus species are identified by gas chromatography (GC) combined with two complementary mass spectrometric methods, namely, electron impact (EI) and chemical ionization at atmospheric pressure (APCI)-mass spectrometry (MS). The APCI source utilizes soft X-radiation, which enables the selective protonation of the volatile metabolites largely without side reactions. Nearly 80 volatile or semivolatile compounds from different substance classes, namely, alcohols, aldehydes, ketones, carboxylic acids, esters, substituted aromatic compounds, alkenes, terpenes, oxidized terpenes, sesquiterpenes, and oxidized sesquiterpenes, could be identified. The profiles of volatile and semivolatile metabolites of the different fungus species are characteristic of them and allow their safe differentiation. The application of the same GC parameters and APCI source allows a simple method transfer from MS to ion mobility spectrometry (IMS), which permits on-site analyses of grain stores. Characterization of IMS yields limits of detection very similar to those of APCI-MS. Accordingly, more than 90% of the volatile metabolites found by APCI-MS were also detected in IMS. In addition to different fungus genera, different species of one fungus genus could also be differentiated by GC-IMS.

Quantitative Estimation of 38 Illicit Psychostimulants in Blood by GC-APCI-QTOFMS with Nitrogen Chemiluminescence Detection Based on Three External Calibrators.

A method was developed for quantitative estimation of illicit psychostimulants in blood, with an emphasis on new psychoactive substances, based on gas chromatography nitrogen chemiluminescence detection coupled with atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry (GC-NCD-APCI-QTOFMS). Quantitative estimation relied on the NCD's N-equimolar response to nitrogen, using amphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and methylenedioxypyrovalerone as external calibrators for prim-, sec- and tert- amines, respectively. After spiking with 38 stimulants at 3 concentration levels, the donor blood samples were submitted to liquid-liquid extraction at a basic pH followed by acylation with trifluoroacetic anhydride. All but 3 psychostimulants could be analyzed with a limit of quantification (LOQ) of 0.05mg/L. At LOQ, the coefficient of variation (CV) values for between-day accuracy was 62.3-143.3% (mean, 93.5%; median, 88.5%) and precision 6.6-22.4% (mean, 15.8%; median, 16.1%). In addition, 11 post-mortem blood samples, containing 0.08-2.4mg/L of amphetamine (n=5), methamphetamine (n=4) or MDMA (n=4), were analyzed by the GC-NCD-APCI-QTOFMS method, and the results were compared with an established electron ionization GC-MS method with appropriate calibration. The agreement between the 2 methods was 62.5-117.3%. Regarding identification, the APCI source permitted detection of the intact precursor ion, or the respective acylation product, for all of the measured compounds. The GC-NCD-APCI-QTOFMS method developed here enables instant quantitative estimation of illicit psychostimulants in blood at reasonable accuracy, without the necessity of possessing the true reference standards for each analyte.

Efficiency of ESI and APCI ionization sources in LC-MS/MS systems for analysis of 22 pesticide residues in food matrix

The intensive use of pesticides has led to the need to optimize analytical methodologies for the control of residues in food. The present study aims to compare the efficiency of different ion sources (Eletrospray Ionization-ESI and Atmospheric Pressure Chemical Ionization – APCI) in LC-MS/MS systems, when analysing 22 pesticides in a cabbage matrix. The method performance was evaluated during a validation study. Organophosphates, triazoles, pyrethroids and triazines compounds showed good linearity in the range 0.5–200 μg.Kg−1. Statistical tests were used to evaluate linearity. LOQm values varied from 0.50 to 1.0 μg.Kg−1 to the ESI source, and 1.0–2.0 μg.Kg−1 for the APCI source. Matrix effect was more intense when using the APCI source. Accuracy and precision were evaluated at three levels of concentration (2; 20 and 100 μg Kg−1). Most of the compounds presented recovery between 70 and 120%. ESI-LC-MS/MS system showed greater efficiency in multiresidue analysis in the cabbage matrix.

Ionization of tocopherols and tocotrienols in atmospheric pressure chemical ionization.

Tocopherols and tocotrienols are chemical compounds insusceptible to the ionization process under atmospheric pressure conditions. Therefore, the selection of the optimal ion source settings for their quantification requires special attention. The aim of this study was to analyse the influence of the APCI source parameters on the response of tocochromanols and two related compounds. Standard solutions of target compounds were injected on the high-performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (HPLC/APCI-MS/MS) system separately and analysed with 30 randomly selected ion source settings. The obtained responses were modelled by multivariate linear regression with least absolute shrinkage and selection operator. The developed models were used to choose the best APCI conditions. Multivariate linear models were built for eight tocochromanols, trolox and BHT. The APCI settings derived from the models did not increase the peak areas obtained for T and T3 during the ionization process. Ionization conditions based on models for trolox and BHT improved analytical responses by 12-36% and 4-32%, respectively. The application of the ion source settings optimal for trolox and BHT to tocochromanols did not result in better analytical responses. The ionization pattern of tocochromanols in the APCI source is problematic and should be further investigated. Modelling methodology for response improvement presented in this study can be applied in similar studies.

A multi-analyte approach to help in assessing the severity of acute poisonings - Development and validation of a fast LC-MS/MS quantification approach for 45 drugs and their relevant metabolites with one-point calibration.

Diagnosis, monitoring of the efficiency of detoxification, and estimating the prognosis of acute poisonings are important tasks in emergency toxicology. Comprehensive screening and quantification of relevant substances by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS) help in assessing the severity of most acute poisonings. Turnaround time for such analyses must be short enough to impact on clinical decisions. Therefore, a multi-analyte LC-MS/MS approach with a 5-minute gradient was developed and validated for 45 drugs and their active metabolites as a complement to an existing GC-MS approach using the same liquid-liquid extraction. The determination ranges were defined by quality control samples of low and high, representing concentrations from low therapeutic to highly toxic levels. To shorten the turnaround time, one-point calibration was used. Validation showed low matrix effects and ionization effects of co-eluting analytes thanks to APCI source as well as sufficient recoveries, precisions, and selectivities. For accuracy, 32 of the 45 compounds fulfilled the criteria for quantification in lower therapeutic and 41 in overdosed and toxic concentrations, considering limits of ±30% deviation. The reuse of the processed calibrator for a period of 30days was possible for 32 compounds, showing sufficient stability at 8°C. In addition, analysis of authentic blood samples showed the applicability and yielded drug levels, which were comparable to those determined by fully validated therapeutic drug monitoring methods. In conclusion, the present approach in combination with the GC-MS approach should provide sufficient support for clinical assessment of the severity of poisonings with 68 compounds in an acceptable turnaround time.

Characterization of nitrated sugar alcohols by atmospheric-pressure chemical-ionization mass spectrometry.

The nitrated sugar alcohols mannitol hexanitrate (MHN), sorbitol hexanitrate (SHN) and xylitol pentanitrate (XPN) are in the same class of compounds as the powerful military-grade explosive pentaerythritol tetranitrate (PETN) and the homemade explosive erythritol tetranitrate (ETN) but, unlike for PETN and ETN, ways to detect MHN, SHN and XPN by mass spectrometry (MS) have not been fully investigated. Atmospheric-pressure chemical-ionization mass spectrometry (APCI-MS) was used to detect ions characteristic of nitrated sugar alcohols. APCI time-of-flight mass spectrometry (APCI-TOF MS) and collision-induced dissociation tandem mass spectrometry (CID MS/MS) were used for confirmation of each ion assignment. In addition, the use of the chemical ionization reagent dichloromethane was investigated to improve sensitivity and selectivity for detection of MHN, SHN and XPN. All the nitrated sugar alcohols studied followed similar fragmentation pathways in the APCI source. MHN, SHN and XPN were detectable as fragment ions formed by the loss of NO2 , HNO2 , NO3 , and CH2 NO2 groups, and in the presence of dichloromethane chlorinated adduct ions were observed. It was determined that in MS/MS mode, chlorinated adducts of MHN and SHN had the lowest limits of detection (LODs), while for XPN the lowest LOD was for the [XPN-NO2 ]- fragment ion. Partially nitrated analogs of each of the three compounds were also present in the starting materials, and ions attributable to these compounds versus those formed from in-source fragmentation of MHN, SHN, and XPN were distinguished and assigned using liquid chromatography APCI-MS and ESI-MS. The APCI-MS technique provides a selective and sensitive method for the detection of nitrated sugar alcohols. The methods disclosed here will benefit the area of explosives trace detection for counterterrorism and forensics. Copyright © 2016 John Wiley & Sons, Ltd.

Multiclass profiling of lipids of archaeological interest by ultra-high pressure liquid chromatography-atmospheric pressure chemical ionization-high resolution mass spectrometry

In the present work, an analytical methodology for the comprehensive evaluation of multiclass lipids (including mono-, di- and triacylglycerols (MAGs, DAGs and TAGs) along with sterols) in archaeological ceramic vessels has been developed. It is based on the use of ultra-high pressure liquid chromatography-atmospheric pressure chemical ionization-high resolution mass spectrometry (UHPLC-APCI-HRMS) with a time-of-flight mass analyser operated in the positive ionization mode. The vaporizer temperature of the APCI source was found to exert a critical influence on the fragmentation exhibited by the different studied TAGs. This fragmentation information combined with accurate mass measurements enabled the unambiguous identification of the targeted species. From the chromatographic side, two different methods were developed using: (i) a 2.1×50mm C18 high-throughput column (1.8μm particle size), with MeOH/H2O 50:50 (v/v) and isopropanol (i-PrOH) as mobile phases and; (ii) a 4.6×150mm C18 high-throughput column (with 1.8μm particle size), with MeOH and i-PrOH as mobile phases. The first method involved a fast 12-min gradient, which enabled a fast and sensitive screening of the lipid content in the studied samples. The second 25-min confirmatory method provided a thorough TAGs separation. Both methods were successfully applied for the comprehensive analysis of lipid traces from archaeological ceramics with LOQs below 5ngg−1 in most cases. The proposed methodology was applied on different ceramic samples, which belong to the Culture of the Iberians (6th–1st ct. BCE).

Elevated urinary levels of carcinogenic N-nitrosamines in patients with urinary tract infections measured by isotope dilution online SPE LC–MS/MS

N-nitrosamines (NAms) are well-documented for their carcinogenic potential. Human exposure to NAms may arise from the daily environment and endogenous formation via the reaction of secondary amines with nitrites or from bacteria infection. We describe the use of isotope dilution online solid-phase extraction (SPE) LC–MS/MS to quantify nine NAms in human urine. This method was validated and further applied to healthy subjects and patients with urinary tract infection (UTI). N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine (NMEA), N-nitrosopyrrolidine (NPYR) and N-nitrosomorpholine (NMOR) were analyzed with an APCI source, while N-nitrosodiethylamine (NDEA), N-nitrosopiperidine (NPIP), N-nitrosodi-n-propylamine (NDPA), N-nitrosodibutylamine (NDBA) and N-nitrosodiphenylamine (NDPhA) were quantified with an ESI source, due to their effect on the sensitivity and chromatography. NDMA was the most abundant N-nitrosamine, while NDPhA was firstly identified in human. UTI patients had three to twelve-fold higher concentrations for NDMA, NPIP, NDEA, NMOR and NDBA in urine than healthy subjects, and the NAms were significantly decreased after antibiotics treatment. NDMA concentrations were also significantly correlated with the pH value, leukocyte esterase activity or nitrite in urines of UTI patients. Our findings by online SPE LC–MS/MS method evidenced that UTI patients experienced various NAms exposures, especially the potent carcinogen NDMA, which was likely induced by bacteria infection.

Pentacyclic triterpene in Olea europaea L: A simultaneous determination by high-performance liquid chromatography coupled to mass spectrometry

Pentacyclic triterpenes are gaining interest due to their beneficial health effects, as anti-inflammatory, anti-diabetic and anti-tumoral, among others. In this study, an analytical LC–MS method was developed for the simultaneous determination of maslinic, oleanolic and ursolic acids along with erythrodiol and uvaol, which are the main triterpenic compounds present in the fruits and leaves of Olea europaea L. A Zorbax Eclipse PAH column at 30°C with mobile phase of water (17%) and methanol (83%) at 0.8mL/min conformed the optimal chromatographic conditions that allowed the separation of the compounds of interest, two pairs of which are isomers differing only in the position of one methyl group (oleanolic–ursolic and erythrodiol–uvaol). The ionization was performed in an APCI source at 450°C programmed in negative mode for the triterpenic acids, and in positive for the alcohols. An ion trap (LC–IT-MS) and a triple quadrupole (LC–QqQ-MS) were assessed for maximal sensitivity that was achieved with LC–QqQ-MS. The LODs of triterpenic acids were lower than 1nM, whereas for erythrodiol and uvaol were 4.5 and 7.5nM, respectively. The method was linear for the five analytes in the range of concentrations from 0.005 to 15μM with correlation coefficients exceeding 0.99. The precision and accuracy were ≤9.90% and ≤9.57%, respectively. The applicability of the validated method was assessed in the analysis of the pentacyclic triterpenes in Marfil table olives, after the optimization of the extraction procedure. The developed method constitutes the first step for future studies of triterpenic compounds present in foods that would allow establishing their effects on human health.

Use of electron ionization and atmospheric pressure chemical ionization in gas chromatography coupled to time-of-flight mass spectrometry for screening and identification of organic pollutants in waters

A new approach has been developed for multiclass screening of organic contaminants in water based on the use of gas chromatography coupled to hybrid quadrupole high-resolution time-of-flight mass spectrometry with atmospheric pressure chemical ionization (GC–(APCI)QTOF MS). The soft ionization promoted by the APCI source allows effective and wide-scope screening based on the investigation of the molecular ion and/or protonated molecule. This is in contrast to electron ionization (EI) where ionization typically results in extensive fragmentation, and diagnostic ions and/or spectra need to be known a priori to facilitate detection of the analytes in the raw data. Around 170 organic contaminants from different chemical families were initially investigated by both approaches, i.e. GC-(EI)TOF and GC-(APCI)QTOF, including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and a notable number of pesticides and relevant metabolites. The new GC–(APCI)QTOF MS approach easily allowed widening the number of compounds investigated (85 additional compounds), with more pesticides, personal care products (UV filters, musks), polychloronaphthalenes (PCNs), antimicrobials, insect repellents, etc., most of them considered as emerging contaminants. Both GC-(EI)TOF and GC-(APCI)QTOF methodologies have been applied, evaluating their potential for a wide-scope screening in the environmental field.

Application of direct atmospheric pressure chemical ionization tandem mass spectrometry for on-line analysis of gas phase of cigarette mainstream smoke

In order to determine the chemical pollutants in cigarette smoke which might possess potential risks to human health and environment, a method coupling smoking machine to atmospheric pressure chemical ionization tandem mass spectrometry (APCI–MS/MS) was developed and applied to on-line analysis of cigarette mainstream smoke. The commercial smoking machine and the ion source of APCI–MS/MS were modified in order to achieve on-line analysis of single puff or puff-by-puff cigarette mainstream smoke. The technique is based on the direct introduction of cigarette smoke into the APCI source via an atmospheric pressure inlet. Four hazardous volatile organic compounds (acrylonitrile, crotonaldehyde, benzene and toluene) were selected for qualitative and quantitative analyses. The results showed that the calibration curves of the four compounds exhibited good linear relations (R2>0.99) with the limits of detection from 0.19 to 2.05ngmL−1 and the relative standard deviation from 3.41% to 8.72%. The developed method is simple, fast, sensitive and repeatable; furthermore, it could provide an alternative way for the determination of a variety of hazardous compounds and for the investigation of the contribution of the cigarette smoke to the pollution of the environment.

Super‐atmospheric pressure chemical ionization mass spectrometry

Super-atmospheric pressure chemical ionization (APCI) mass spectrometry was performed using a commercial mass spectrometer by pressurizing the ion source with compressed air up to 7 atm. Similar to typical APCI source, reactant ions in the experiment were generated with corona discharge using a needle electrode. Although a higher needle potential was necessary to initiate the corona discharge, discharge current and detected ion signal were stable at all tested pressures. A Roots booster pump with variable pumping speed was installed between the evacuation port of the mass spectrometer and the original rough pumps to maintain a same pressure in the first pumping stage of the mass spectrometer regardless of ion source pressure. Measurement of gaseous methamphetamine and research department explosive showed an increase in ion intensity with the ion source pressure until an optimum pressure at around 4-5 atm. Beyond 5 atm, the ion intensity decreased with further increase of pressure, likely due to greater ion losses inside the ion transport capillary. For benzene, it was found that besides molecular ion and protonated species, ion due to [M + 2H](+) which was not so common in APCI, was also observed with high ion abundance under super-atmospheric pressure condition.

Simultaneous quantification of cefpodoxime proxetil and clavulanic acid in human plasma by LC–MS using solid phase extraction with application to pharmacokinetic studies

A simple, rapid and selective high performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS) method was developed and validated for the simultaneous estimation of cefpodoxime proxetil (CDPX) and clavulanic acid (CA) in human plasma. Extraction of samples was done by solid phase extraction technique (SPE) and chloramphenicol used as internal standard. Chromatographic separation was carried out on a reverse phase Princeton SPHER C18 (150mm×4mm i.d., 5μm) column using mixture of methanol: acetonitrile: 2mM ammonium acetate (25:25:50, v/v, pH 3.5) at 0.8mL/min flow rate. Detection was performed on a single quadrupole MS by selected ion monitoring (SIM) mode via APCI source. The calibration curve was linear within the concentration range, 0.04-4.4μg/mL and 0.1-10.0μg/mL for CDPX and CA respectively. Pharmacokinetic parameters of tablet (CDPX 200mg, CA 125mg) were evaluated. Cmax, Tmax, T1/2, elimination rate constant (Kel), AUC0-t, and AUC0-∞ of tablet were 2.13±0.06μg/mL, 2h, 3.05±0.15h, 0.24±0.37h(-1), 6.81±0.14μg h/mL and 7.72±0.23μg h/mL respectively for cefpodoxime (CP), 5.34±0.28μg/mL, 2h, 2.73±0.25h, 0.26±0.31h(-1), 15.37±0.16μg h/mL and 16.59±0.53μg h/mL respectively for CA.