Atmospheric Pressure Chemical Ionization Mode Research Articles

Alkaloids from Siparuna (Siparunaceae) are predicted as the inhibitors of proteolysis and plasma coagulation caused by snake venom and potentially counteract phospholipase A2 activity of Bothrops jararaca

Ethnopharmacological relevanceSnakebite envenomation (SBE) is the world's most lethal neglected tropical disease. Bothrops jararaca is the species that causes the greatest number of SBEs in the South and Southeastern of Brazil. The main symptoms are local (inflammation, edema, hemorrhage, and myonecrosis) and systemic (hemorrhage, hemostatic alterations with consumptive coagulopathy, and death) effects. Species of the genus Siparuna, Siparunaceae, are used in folk and traditional medicine to treat SBE. However, limited information is available concerning Brazilian Siparuna species against SBE. Aim of the studyTo investigate the correlation between the compounds present in the extracts of five Siparuna species as potential agents against proteolytic activity, plasma coagulation, and phospholipase A2 (PLA2) activity caused by B. jararaca venom, using data obtained by UHPLC-MS/MS, biological activity, and multivariate statistics. Materials and methodsThe ethanol extracts from leaves of S. ficoides, S. decipiens, S. glycycarpa, S. reginae, and S. cymosa were fractionated by liquid-liquid extraction using different solvents of increasing polarity (hexane, dichloromethane, ethyl acetate, and n-butanol), affording their respective extracts, totaling 25 samples that were assayed through in vitro plasma coagulation and proteolytic activity assays. Moreover, the extracts were analyzed by UHPLC-MS/MS, using electrospray ionization (ESI) and atmospheric-pressure chemical ionization (APCI) in negative and positive ionization modes. The data was processed in MZmine v. 2.53 and evaluated by multivariate statistical tests (PLS) using the software UnscramblerX v. 10.4. These data were also used to build molecular networks (GNPS), and some ions of interest could be annotated using the library of molecules on the GNPS platform. ResultsA total of 19 extracts inhibited B. jararaca-induced plasma coagulation, with emphasis on S. cymosa and S. reginae (800 s). The inhibition of the proteolytic activity was also promising, ranging from 16% (S. glycycarpa) to 99% (S. cymosa, S. decipiens, and S. reginae). In addition, most extracts from S. cymosa and S. reginae inhibited 70–90% of PLA2 activity. Based on data from positive mode APCI analyses, it was possible to obtain a statistic model with reliable predictive capacity which exhibited an average R2 of 0.95 and a Q2 of 0.88, indicating a robust fit. This process revealed five ions, identified as the alkaloids: coclaurine (1), stepholidine (2) O-methylisopiline (3), nornantenine (4) and laurolitsine (5). This is the first study to evidence the potential antivenom of alkaloids from Siparuna species. ConclusionsAltogether, our results give support to the popular use of Siparuna extracts in SBE accidents, suggesting their potential as an alternative or complementary strategy against envenoming by B. jararaca venom. The predicted ions in the chemometric analysis for the assayed activities can also be correlated with the blocking activity and encourage the continuation of this study for possible isolation and testing of individual compounds on the used models.

Self-aspiration sampling design for rapid analyses of volatile organic compounds based on atmospheric pressure chemical ionization/photoionization combined ionization source mass spectrometry.

Development of combined mass spectrometry ionization sources has enabled expansion of the application and scope of mass spectrometry. A novel hybrid ionization system combining vacuum ultraviolet (VUV) and atmospheric pressure chemical ionization (APCI) was constructed. Gaseous samples were self-aspirated into an ionization zone through a capillary by negative pressure, generated by high-speed airflow based on the Venturi effect. Compared with APCI mode alone, the signal-to-noise ratio (S/N) in APCI/VUV mode was increased by about 276-times. To increase the ionization efficiency further, correlated experimental conditions were optimized. Four types of volatile organic compounds (VOCs) were tested to evaluate the performance of the APCI/VUV ion source. Excellent linearity and limit of detection were achieved for compounds in mixed solutions. Quantitative analyses of four VOCs (toluene, cyclohexanone, styrene and ethylbenzene) using APCI/VUV-MS were done, and the relative standard deviations (RSDs) were 1.57%, 6.30%, 4.49% and 8.21%, respectively, indicating that the APCI/VUV ionization source had excellent reproducibility. Our results demonstrated that the developed method was promising for analyzing VOCs as well as being rapid, simple, and easy to operate.

Exposure and human health risk assessment of chlorinated paraffins in indoor and outdoor dust from a metropolitan city, Lahore, Pakistan

Chlorinated paraffins (CPs) are widely used in commercial products due to their stability and durability and are subsequently released in the environment posing serious health risks in human population. In this study, dust samples from indoor and outdoor settings of residential, commercial and industrial zones as well as from vehicles were collected from a metropolitan city, Lahore, Pakistan. A total of 83 dust samples were analyzed for short (SCCPs) and medium (MCCPs) chained CPs through quadrupole time of flight mass spectrometer in atmospheric pressure chemical ionization (APCI QToF-MS) mode. The median concentrations of ƩCPs (C10-17) in outdoor dust were higher than indoor dust in industries (0.97 vs 0.48 μg/g), and residential areas (0.70 vs 0.13 μg/g) while lower in commercial areas (0.28 vs 0.44 μg/g) reflecting their higher prevalence in industrial and residential zones. The vehicular dust had median ƩCPs of 0.16 μg/g which was similar to residential indoor dust. Overall, ƩSCCPs were dominant among all zones with C10,12 and Cl7-8 as abundant carbon and chlorine congeners in both indoor and outdoor dusts. No significant correlations were observed between indoor and outdoor dust for ƩSCCPs and ƩMCCPs indicating their varying exposure. Health hazard index and margin of exposure revealed that toddlers were at higher risk compared to adults as a results of CPs exposure from both indoor and outdoor environments. This is the first ever assessment of CPs in Pakistan reflecting higher prevalence of SCCPs than MCCPs in dust of local environment posing some serious health consequences hence needed intensive investigation and effective management.

Insight into in silico prediction and chemical degradation study of osimertinib mesylate by LC-HRMS and NMR: Investigation of a typical case of alkaline pH-mediated oxidative degradation product

Osimertinib mesylate is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor used to treat nonsmall-cell lung cancer. The objective was to understand in silico prediction and chemical-based stress testing of the osimertinib mesylate. A total of eight degradation products (DPs) were formed under chemical stress testing. An in silico tool viz., Zeneth predicted a higher percentage of DPs. The separation of all the DPs was achieved using reversed phase high-performance liquid chromatography, employing X-Bridge C18 column with ammonium acetate (pH adjusted to 7.50 with ammonia) and acetonitrile as mobile phase. The overall results showed it underwent significant degradation in acidic, alkaline, and oxidative conditions. In rest of the conditions, osimertinib mesylate was found to be stable or slight degradation was observed in photolytic condition. The structure of DPs was elucidated with a comparison of data generated from high-resolution mass spectrometry (HRMS) of osimertinib mesylate and its degradation products. To confirm the unambiguous regioisomers, one-dimensional (1D) and two-dimentional (2D) nuclear magnetic resonance studies were performed. Furthermore, the N-oxide position was assigned for the first time using the Meisenheimer rearrangement reaction in atmospheric pressure chemical ionization mode. Interestingly, an unusual reaction of DP2 formation was observed at alkaline conditions. In silico tools such as DEREK and Sarah predicted osimertinib mesylate and most of the DPs found to be structural alert for mutagenicity.

Comparison of APCI orbitrap MS and GCxGC/EI TOF MS for the hydrocarbon analysis of heavy base oils

The performance of positive-ion mode atmospheric pressure chemical ionization linear quadrupole ion trap orbitrap mass spectrometry (APCI LQIT Orbitrap MS) has been compared to that of two-dimensional gas chromatography coupled with positive-ion mode electron ionization time-of-flight mass spectrometry (GCxGC/EI TOF MS) for the analysis of group III heavy base oils. Upon APCI, all compounds were predominantly ionized via protonation. However, protonated alkanes are not stable and predominantly generated [M−H]+ ions via elimination of a hydrogen molecule from the protonated molecule. The high-resolution APCI mass spectra provided elemental composition information for the compounds while low-resolution APCI mass spectra were used for semiquantitative evaluation of the relative amounts of the compounds. Ions corresponding to compounds in seven hydrocarbon classes, i.e., (1) linear and branched alkanes, (2) monocycloalkanes, (3) dicycloalkanes, (4) tricycloalkanes and alkylbenzenes, (5) tetracycloalkanes, (6) pentacycloalkanes, and (7) hexacycloalkanes were identified. On the other hand, the GCxGC/EI TOF MS method enabled the chromatographic separation of most analytes. The measured EI mass spectra were used for the identification of the compounds while the GC peak areas were used for semiquantitative evaluation. The detected compounds were classified into three different hydrocarbon classes, (1) linear and branched alkanes, (2) cycloalkanes, and (3) aromatic hydrocarbons. The (+)APCI LQIT Orbitrap MS method was found to be faster and to provide more information for the larger compounds in the samples. For example, polycycloalkanes were only detected by using (+)APCI MS. However, no aromatic compounds were detected. Data processing was more straightforward than when using the GCxGC/EI TOF MS method. However, the latter method provided more accurate results for aromatic hydrocarbons and small alkanes as the analysis of small alkanes by using (+)APCI MS is limited due to the fact that [M−H]+ ions of small alkanes overlap with alkane fragment ions. Both light and heavy aliphatic and aromatic hydrocarbons were detected by using the GCxGC/EI TOF MS method but not polycycloalkanes. Therefore, these two methods complement each other, and each has different strengths and weaknesses.

Inter-laboratory study on simultaneous quantification of ten trichothecenes in feed.

An inter-laboratory study was performed in eight laboratories to evaluate the simultaneous quantification method for HT-2 toxin (HT-2), T-2 toxin (T-2), diacetoxyscirpenol (DAS), neosolaniol (NES), 3-acetyldeoxynivalenol (3-AcDON), 15-acetyldeoxynivalenol (15-AcDON), deoxynivalenol (DON), deoxynivalenol-3-glucoside (D3G), nivalenol (NIV), and fusarenon-X (FUS-X) in feed. The mycotoxins in the samples were extracted with hydrous acetonitrile, purified using a multifunctional column (InertSep® VRA-3) and a phospholipid removal column (Hybrid SPE®-Phospholipid), and then quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with atmospheric pressure chemical ionisation mode. The mean recovery, repeatability, reproducibility, and Horwitz ratio from the inter-laboratory validation study were 99.8-109%, 3.1-9.8%, 4.3-9.8%, and 0.19-0.45, respectively, for type A trichothecenes (HT-2, T-2, DAS, and NES). Those values for type B trichothecenes (3-AcDON, 15-AcDON, DON, NIV, and FUS-X) were 89.9-116%, 3.4-9.1%, 5.6-14%, and 0.25-0.70, and the values for modified mycotoxin (D3G) were 78.2-96.7%, 3.5-6.4%, and 13-22%, respectively.

Analysis of Near 400 Pesticides in Tea via LC–MS/MS: Simple Sample Preparation and APCI to Improve Analyte Coverage

As regulatory laboratories search for and implement consolidated methods for multiple matrix and analyte classes, compound lists increase to hundreds or thousands of targets. Multi-instrument approaches are often relied upon to analyze all pesticide targets, with the workload split between liquid chromatography–mass spectrometry (LC–MS) and gas chromatography–mass spectrometry (GC–MS) instrumentation. In this work, a simple solvent extraction approach was coupled with dual source electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) modes on an LC–tandem mass spectrometry (MS/MS) instrument to analyze 395 analytes extracted from black tea (345 compounds via ESI and 50 compounds via APCI, along with the internal standards). Excellent method performance (defined as an accuracy of 70–120% and a precision of <20% at one of two validation levels) was achieved for over 93% of analytes, including compounds normally analyzed by GC–MS, such as trifluralin, chlorfenson, chlormephos, fenchlorphos, etridiazole, and others. This approach can allow the consolidation of a pesticide method to a single instrument or significantly reduce the workload of a complementary GC–MS method.

Development of an analytical method for the determination and quantification of n-nitrosodimethylamine in olmesartan by HPLC-MS/MS

In this study, a simple, rapid, and highly sensitive analytical method has been developed and validated for the detection, separation, and quantification of N-nitrosodimethylamine in the active pharmaceutical ingredient olmesartan medoxomil, as well as in manufactured tablets and marketed tablets, using high-performance liquid chromatography-mass spectrometry. Chromatographic separation was achieved using the Agilent Eclipse XDB-C18 column (5 m × 4.6 mm × 150 mm) with a binary gradient with water as mobile phase A and 0.1 % formic acid in methanol as mobile phase B, flow rate 0.5 mL/min, B. Due to the presence of polar groups, N-nitrosodimethylamine is successfully ionized and quantified in positive atmospheric pressure chemical ionization mode using multiple reaction monitoring. The method was validated according to International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines, evaluating the limit of detection and quantification, a good signal-to-noise ratio, and an excellent regression coefficient greater than 0.995 were found. The accuracy (expressed as recovery) of the method was performed in triplicate obtaining satisfactory results between 80 and 104 %, with a precision (%RSD) of 0.34 – 1.50 %. The method can be used routinely for the determination and quantification of N-nitrosodimethylamine in olmesartan.

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) Method for the Quantification of Steroids Androstenedione, Dehydroepiandrosterone, 11-Deoxycortisol, 17-Hydroxyprogesterone, and Testosterone.

Congenital adrenal hyperplasia (CAH) is a group of autosomal-recessive disorders due to deficiency of 11- or 21-hydroxylase. The analysis of cortisol, androstenedione, 17-hydroxyprogesterone (OHPG), dehydroepiandrosterone (DHEA), 11-deoxycortisol, and testosterone is generally performed in the diagnosis and/or follow-up of CAH. Analysis of specific steroids is also performed in other disorders such as evaluation of hirsutism or infertility in females and hypogonadism in males. Cortisol is generally analyzed by immunoassays, whereas other hormones are preferably assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A multiple reaction monitoring, positive mode atmospheric pressure chemical ionization, LC-MS/MS method is described for the simultaneous quantification of androstenedione, 17-hydroxyprogesterone, DHEA, 11-deoxycortisol and testosterone. The method involves addition of labeled internal standards to serum samples and extraction of steroids in methyl tert-butyl ether. The extract is evaporated under stream of nitrogen, and the residue is reconstituted in methanol and analyzed by LC-MS/MS.

Measurement of Urinary Free Cortisol and Cortisone by LC-MS/MS.

Monitoring urinary free cortisol (UFC) excretion helps assess adrenal function and is used to screen for endogenous Cushing's syndrome caused by an adrenal or pituitary tumor. While serum cortisol levels fluctuate in response to time of day, stress, and concentrations of cortisol-binding globulin (CBG), a 24-h urine collection measures the cortisol produced over the entire day and does not suffer from as much variability as a serum measurement.We describe here a method of measurement of urinary free cortisol (UFC) and cortisone using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Urine samples, combined with stable isotope-labeled internal standards, are extracted by liquid-liquid extraction using ethyl acetate and hexane. An API 5500 mass spectrometer operated in positive atmospheric pressure chemical ionization (APCI) mode is used for detection.

Fast Determination of the Lignin Monomer Compositions of Genetic Variants of Poplar via Fast Pyrolysis/Atmospheric Pressure Chemical Ionization Mass Spectrometry.

The proportional content of the phenylpropanoid monomeric units (4-hydroxyphenyl (H), guaiacyl (G), and syringyl (S)) in lignin is of paramount importance in germ plasm screening and for evaluating the results of plant breeding and genetic engineering. This content is usually determined using a tedious and slow (2 days/sample) method involving derivatization followed by reductive cleavage (DFRC) combined with GC/MS or NMR analysis. We report here a fast mass spectrometric method for the determination of the monomer content. This method is based on the fast pyrolysis of a lignin sample inside the ion source area of a linear quadrupole ion trap mass spectrometer. The evaporated pyrolysis products are promptly deprotonated via negative-ion mode atmospheric pressure chemical ionization ((-)APCI) and analyzed by the mass spectrometer to determine the monomer content. The results obtained for the wild-type and six genetic variants of poplar were consistent with those obtained by the DFRC method. However, the mass spectrometry method requires only a small amount of sample (50 μg) and the use of only small amounts of three benign chemicals, methanol, water, and ammonium hydroxide, as opposed to DFRC that requires substantially larger amounts of sample (10 mg or more) and large amounts of several hazardous chemicals. Furthermore, the mass spectrometry method is substantially faster (3 min/sample), more precise, and the data interpretation is more straightforward as only nine ions measured by the mass spectrometer are considered.

A novel dual ionization modality source for infrared laser ablation post-ionization mass spectrometry imaging to study fungicide metabolism and transport

We present a novel probe design for ambient laser-based mass spectrometry imaging combining electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) in a single probe, compatible with a commercial laser ablation electrospray ionization (LAESI) instrument. Here we describe the probe design considerations and features, as well as an in-house developed data processing routine designed to extract accurate mass spectrometry imaging data from ambient laser ablation post-ionization experiments. We characterize the probe performance in both APCI and ESI mode on a selection of compounds and show improved pixel-to-pixel repeatability for LA-APCI as compared to LAESI. We apply the dual ionization probe in APCI mode in a time series experiment to monitor agrochemicals on tomato plants. We investigate the translocation of fungicide isotianil and one of its metabolites, anthranilonitrile, by mass spectrometry imaging over a period of two weeks after application on a leaf surface. LA-APCI-MSI shows translocation of anthranilonitrile from treated leaves towards non-treated leaves. In summary, we demonstrate that LA-APCI imaging is a valuable addition to the ambient mass spectrometry toolbox, with particular advantages for imaging experiments across a variety of compounds.

Identification and structural characterization of potential degraded impurities of ribociclib by time of flight -tandem mass spectrometry, and their toxicity prediction

The US FDA and EMA approved Ribociclib (RIBO) to treat metastatic breast cancers in 2017. Formation of impurities during storage of any drug can significantly contribute to its overall toxicity and therapeutic efficacy, which ultimately leads to a safety concern. Over the period, it has been observed that impurities sometimes cause serious unwanted toxicity, which can even lead to withdrawal of a drug from market. Therefore, complete characterization of potential impurities is extremely important to identify molecular hot spots regarding structural changes. To the best of our knowledge, till date, the potential degraded impurities of RIBO are unknown. No study reported in literature on the structural characterization of the degradation impurities of RIBO. In this study, an ICH recommended comprehensive stress study under hydrolytic, oxidative, photolytic and thermolytic conditions was performed on RIBO. The degradation products were characterized by tandem mass spectrometry utilising time of flight mass analyzer majorly after electrospray ionisation. The atmospheric pressure chemical ionisation mode was employed in characterization of the N-oxide degradation products where Meisenheimer rearrangement occurred. A degradation product was synthesized in house and fully characterized with the help of NMR (1H NMR, 13C NMR, DEPT, 2D NMR and D2O exchange experiments). The source of formylation for the generation of degradation products was investigated employing different solvent systems. The degradation pathways were delineated by explaining the putative mechanism of degradation in various conditions. The in silico toxicity of the degradation impurities was evaluated with the help of ProTox-II toxicity prediction platform.

Isolation, method development, and validation of diterpenes in coffee oil: identification by multiple reaction monitoring approach with atmospheric pressure chemical ionization mode

Pharmacognosy Research,2021,13,1,42-48.DOI:10.4103/pr.pr_66_20Published:April 2021Type:Original ArticleAuthors:Naveen Puttaswamy, Lingaraju Harakanahalli Basavegowda, Deepak Machettira, Chandrappa Siddappa, Rashmi Ramesh, and Shyam Prasad Kodimule Author(s) affiliations:Naveen Puttaswamy1, Lingaraju Harakanahalli Basavegowda2, Deepak Machettira2, Chandrappa Siddappa2, Rashmi Ramesh1, Shyam Prasad Kodimule2 1Analytical Research and Development, Vidya Herbs Pvt. Ltd, Bengaluru, Karnataka, INDIA 2Phytochemistry Lab, Vidya Herbs Pvt. Ltd., Bengaluru, Karnataka, INDIA Abstract:Objectives: The aim of the present study is to isolation, identification, and quantification of free diterpenes in coffee oil of Coffea arabica. Materials and Methods: For the isolation of free diterpenes, saponification reaction step was employed and followed with a liquid-liquid extraction procedure applied. Cafestol and kahweol were identified by multiple reaction monitoring (MRM) of positive ionization (MRM) mode of atmospheric pressure chemical ionization (APCI) mass spectrometry detection. The quantification of free diterpenes was done by high-performance liquid chromatography with diode array detector. The developed method was validated according to the international conference on harmonization guidelines. Results: The ion transitions of the precursor to the product ion at (M + H)+ m/z 317.20→146.90, 281.00, 299.00 for cafestol and 315.10→144.90, 278.90, 296.90 for kahweol were observed. The proposed method was validated for linearity with excellent correlation coefficient of cafestol and kahweol were found to be 0.9997 and 0.9996, respectively. The intra-day and intermediate precisions and repeatability showed the percentage relative standard deviation was <1%. The recovery rate for cafestol and kahweol were observed to be in the acceptable limit of 95.303%–98.539% and 95.963%–97.174%, respectively. The limit of detection of cafestol and kahweol were found to be 6.81 and 7.35 ppm, respectively. The limit of quantitation (LOQ) was found to be 22.72 and 24.52 ppm, respectively. Conclusion: The developed method is simple, rapid, precise, accurate and it is recommended for efficient assays in routine work. Keywords:Atmospheric pressure chemical ionization, Cafestol, Coffea arabica, Kahweol, Method validationView:PDF (1.44 MB)

SAT-LB13 Clinical Utility of 21-Deoxycortisol in Congenital Adrenal Hyperplasia

Introduction Congenital Adrenal Hyperplasia (CAH) is most often caused by mutation of the 21-hydroxylase gene (CYP21), which results in underproduction of cortisol with overproduction of precursor steroids and their metabolites by the adrenal glands. Historically the most common biomarker used for detecting CAH in pediatric patients is 17-Hydroxyprogesterone (17OHP). Another less commonly used biomarker for 21-Hydroxylase deficiency is 21-deoxycortisol (21DOF), which increases from very low levels in normal patients to high levels in affected patients as 17OHP rises to very high levels. In this study we performed retrospective analysis of serum 21DOF concentration in specimens that had been genotyped for mutations in the CYP21A2 gene, or had been submitted to our laboratory for provocative adrenocorticotropin (ACTH / Cosyntropin) stimulation testing. Methods: Biochemical testing for 21DOF concentration was measured by LC-MS/MS. Briefly, a TX-4 HPLC system (Thermo-Fisher) with Agilent® 1100 pumps (Agilent Technologies, Inc.) and a Sciex® 5000 (Danaher) triple quadrupole mass spectrometer in positive mode atmospheric pressure chemical ionization (APCI) was used for detection in Multiple Reaction Monitoring (MRM) mode. Genetic testing was performed using the CAHDetx test, which detects the 12 most common small mutations and large gene deletions/conversions in CYP21A2. Genetic Correlations: 21DOF was quantifiable (above the LLOQ of the assay) in 4% (n=24/600) of specimens where no mutation was detected. 21-DOF was quantifiable in 42% (122/292) of specimens with 21-hydroxylase enzyme mutations as determined by the CAHDetx test. Those mutations included In2G, I172N, V281L and others. Some mutations such as Q318X did not result in a detectable increase in 21-deoxycortisol. ACTH Stimulation Response: 21-deoxycortisol was below the quantitation limit in both the baseline and stimulated samples in ~35% (52/148) of submitted samples. The 21-deoxycortisol was quantifiable in only the stimulation sample in ~45% (65/148) of ACTH stimulation submitted, and was quantifiable in both baseline and stimulated samples in the remaining ~20% (30/148) of ACTH stimulation pairings. The extent of 21-deoxycortisol increase ranged from 1.2-fold to 116-fold with a median 14-fold increase. Clinical Significance: The use of 21-deoxycortisol may be beneficial in reducing the rate of false positives in CAH diagnosis when used in concert with other steroid hormones, and may eventually reduce the need for provocative testing to confirm CAH diagnosis.

Investigation of chromatographic peak broadening in supercritical fluid chromatography/atmospheric pressure chemical ionization mass spectrometry.

Multimode ionization source allows for switching between different ionization techniques, for example, electrospray and atmospheric pressure chemical ionization, within a single analysis. Supercritical fluid chromatography can handle a wide polarity range of substances from hydrophilic to lipophilic in a single run and can undoubtedly benefit from versatility of this ion source. Nevertheless, we observed a significant chromatographic peak broadening effect in atmospheric pressure chemical ionization mode during supercritical fluid chromatography-mass spectrometry analysis of volatile flavor compounds with a dual ion source named ESCi (Waters). Surprisingly, this effect was not related to the separation process but was triggered solely by the ion source conditions. Neither of photodiode array detector, electrospray mode nor a dedicated atmospheric pressure chemical ionization source suffered from such a phenomenon. Chromatographic peak profiles of ten test substances obtained with the dual ion source were compared with photodiode array detector data as a reference. The broadening effect was more pronounced for volatile compounds with low polarity. Dependence of peak broadening on the ion source settings was systematically investigated. Tuning of desolvation gas flow and its temperature dramatically reduced peak distortion and increased detection sensitivity.

Study on the Cure Behavior of a Novel Photocurable Material Using UPLC-Q-TOF-MS

An UPLC-Q-TOF-MS method is developed for cure degree measurement and cure behavior analysis on a novel photocurable adhesive material which is composed of specially designed acrylate oligomers, acrylate monomers, photo-initiators and additives such as ultra-violet absorbent, antioxidant stabilizer, optical stabilizer, etc. The photocurable adhesive material, in both cured and uncured state, were separated by Ultra-Performance Liquid Chromatography (UPLC) and the low molecular weight components were detected and determined quantitatively by high resolution Quadrupole Time-Of-Flight mass spectrometry (Q-TOF-MS) under Atmosphere Pressure Chemical Ionization (APCI) mode. Cure behaviors of all photo-reactive components in the photocurable adhesive material such as acrylate monomers and photo-initiators were studied by quantitatively measuring the amount of each reactive components in different stages of curing. Both the conversion of each acrylate monomers and photo-initiators at different curing energy conditions were calculated and discussed. Nearly full cure was obtained at cure energy of 200 mJ/cm2 for 4-hydroxybutyl acrylate and acryloyl morphine, as well as the two bifunctional monomers, 1,6-hexandiol diacrylate and dimethylol tricyclodecane diacrylate. Only 42.7% and 85.0% conversion were achieved for benzyl acrylate and isobornyl acrylate, respectively while consumption of TPO, a photo-initiator, was 38.0% at this cure energy. The results showed that a minimum 2000 mJ/cm2 energy condition is needed to achieve full cure of all acrylate monomers and enough decomposition of photo-initiator. This study indicated that UPLC-Q-TOF-MS is an effective and precise analytical method for cure degree measurement and cure behavior analysis on the photocurable materials.

Quantitative Analysis of Eight Triterpenoids and Two Sesquiterpenoids in Rhizoma Alismatis by Using UPLC-ESI/APCI-MS/MS and Its Application to Optimisation of Best Harvest Time and Crude Processing Temperature.

Rhizoma Alismatis (RA), widely known as “Ze-Xie” in China, is the tuber of Alisma orientale (Sam.) Juzep (Alismaceae), a Chinese herbal medicine that has been used to treat hyperlipidemia, diabetes, hypertension, dysuria, and inflammation. In this study, a sensitive and reliable method based on an ultra-performance liquid chromatography (UPLC) couple with two ionisation modes, including electrospray ionisation (ESI) and atmospheric pressure chemical ionisation (APCI) tandem mass spectrometry (MS), namely, UPLC-ESI/APCI-MS/MS was developed and validated to simultaneously determine 8 triterpenoids (ESI mode) and 2 sesquiterpenoids (APCI mode) in RA. Ten marker compounds were analysed with a Waters' CORTECS UPLC C18 column (200 mm × 2.1 m, 1.6 μm) and gradient elution with water (contained 0.1% formic) and acetonitrile within 7 min. The established method was validated for linearity, intra- and interday precisions, accuracy, recovery, and stability. The calibration curve for 10 marker compounds showed good linear regression (r > 0.9971). The limits of detection and quantification for analytes were 0.14–1.67 ng/mL and 0.44–5.65 ng/mL, respectively. The relative standard deviations (RSD, %) and accuracy (RE, %) of intra- and interday precisions were less than 3.83% and 1.21% and 3.22% and 1.46%, repeatability and stability for real samples were less than 2.78% and 3.19%, respectively. All recoveries of the 10 marker compounds ranged from 97.24% to 102.49% with RSDs less than 4.05%. The developed method efficiently determined the 10 marker compounds in RA and was subsequently applied to optimise harvest time and crude processing temperature. The result indicated the 90% wilted phase and 70°C (or lower) may be the best harvest time and the processing temperature of RA.

Overcoming the Charged Ion Competition in Triple Quad Chemical Ionization Ion Source for Estimation of Celecoxib in Biological Matrix and its Application to Bioequivalence Study.

The purpose of the study was to develop and validate a sensitive, selective and reproducible method for the estimation of Celecoxib in human plasma. During the development, ion competition phenomenon observed in electrospray ionization ion source of liquid chromatography mass spectrometer system and in order to overcome it, different approaches applied. The Celecoxib and Celecoxib D7 in plasma were extracted by liquid-liquid extraction and separated in less than 4.0 min on a reverse phase C18 column, using isocratic elution with a binary mobile phase in the ratio of 70:30 v/v (Acetonitrile: 0.1% Ammonia Solution). Mass spectrometer was used as detector to quantitate the analytes in positive ion mode, using Atmospheric Pressure Chemical Ionization mode. Since the method was developed to perform the pharmacokinetic end point study for United States and Europe market, the method was fully validated, complying Food and Drug Administration, European Medicines Agency guideline and recommendations of American Association of Pharmaceutical Scientists white papers.

An Automated Method for Chemical Composition Analysis of Lubricant Base Oils by Using Atmospheric Pressure Chemical Ionization Mass Spectrometry.

Since its invention in the 1950s, field ionization mass spectrometry (FI MS) has been, and currently is, the go-to technique employed by the petrochemical industry for the identification of the different types of nonvolatile compounds in their products. Unfortunately, FI MS has several inherent drawbacks, such as poor reproducibility. The performance of positive-ion mode atmospheric pressure chemical ionization mass spectrometry (APCI MS) with O2 gas as the sheath/auxiliary gas and a saturated hydrocarbon solvent/reagent was recently compared with that of FI MS and found to show promise as an alternative, highly reproducible method for lubricant base oil analysis. We report here on the automation of the APCI/O2/saturated hydrocarbon MS method. Isooctane was chosen as the optimal APCI solvent/reagent for base oil ionization due to the low level of fragmentation it provided for model compound mixtures. Three minutes was determined to be the shortest possible cleaning time between samples, regardless of the base oil viscosity. The total analysis time for each sample was 5 min. The reproducibility of the method was assessed by determining within-day and between-day precisions and total precision for hydrocarbon class distributions measured for three different base oils. All total precision values were found to be better than 6.2%, suggesting that the automated (+)APCI/O2/isooctane method is reproducible and robust.