Formic Acid In Water Research Articles

A Vacuum Ultraviolet Photoionization Mass Spectrometry and Density Functional Calculation Study of Formic Acid-Water Clusters.

The interaction between formic acid (FA) and water (W) holds significant importance in various chemical processes. Our study combines vacuum-ultraviolet photoionization mass spectrometry with density functional calculations to investigate formic acid water clusters generated in supersonic molecular beams. The mass spectra obtained reveal the formation of protonated clusters as the major product. Enhanced intensities are observed in the mass spectra for a number of clusters holding the following composition, FA1W5H+, FA2W4H+, FA3W3H+, FA4W2H+, FA5W1H+ and FA6W2H+ compared to their neighbors with one less or one more water component. Our calculations shed light on these potentially stable structures, highlighting cyclic arrangements with molecules enclosed within the ring as the most stable structures, and demonstrate a decrease in the stability upon the addition of a water molecule. Comparing experimental appearance energies with calculated ionization energies suggests that fragmentation can occur from clusters of various sizes.

LC-ESI-MS/MS methods for the quantification of hydrazine mono lactose adduct and hydrazine di lactose adduct in isosorbide dinitrate and hydralazine hydrochloride tablets

Isosorbide dinitrate and hydralazine hydrochloride tablets treat heart failure in addition to conventional therapy, prolong hospitalization for heart failure, and enhance patient-reported functional status. LC-MS/MS methods developed and validated separately for the quantification of hydrazine mono-lactose adduct and hydrazine di-lactose adduct impurities in the isosorbide and hydralazine hydrochloride tablets. Separation of hydrazine mono-lactose adduct impurity achieved on ZIC-HILIC (100 × 4.6 mm, 5 µm) column with 0.1% formic acid in water as mobile phase A and acetonitrile as mobile phase B. The HPLC method gradient elution is; Tmin/% of B: 0/90, 15/40, 15.1/90, and 20/90. The flow rate is 1.0 mL per minute, and the injection volume is 20 µL. Separation of hydrazine di-lactose adduct impurity achieved on Inertsil HILIC (150 × 4.6 mm, 5 µm) column with 10 Mm ammonium acetate in water as mobile phase A and acetonitrile as mobile phase B. The HPLC method gradient elution is; Tmin/% of B: 0/90, 15/40, 15.1/90, and 18/90. The flow rate is 1.0 mL per minute, and the injection volume is 40 µL. Method validation has demonstrated both methods are specific, sensitive, linear, precise, accurate, stable and robust.

A multianalyte LC-MS/MS method for accurate quantification of Nitrosamines in Olmesartan tablets

This research summaries the development, optimization and validation of liquid chromatography tandem mass spectrometric (LC-MS/MS) method for concurrent measurement of seven nitrosamines viz; NDMA, NDEA, NDIPA, NDPA, NEIPA, NMPA & NMBA in Olmesartan tablet. Controlling these nitrosamines at trace levels is imperative for ensuring the safety of drug substances and products for consumption. Various regulatory authorities stress the significance of utilizing highly sensitive analytical methods to precisely measure nitrosamines at trace levels. The method applied effective chromatographic separation and optimized parameters for mass spectrometric detection. Detection was carried out using APCI positive ion mode. Chromatographic separation was achieved using a Thermo Accucore PFP column (150 mm x 4.6 mm, 2.6 µ), with a simple gradient elution of mobile phase consisting of 0.1 % formic acid in water (mobile phase A) and methanol (mobile phase B). The total run time was 20 min, with a flow rate of 0.800 mL/min.The method was validated according to the International Council on Harmonisation (ICH Q2 (R2)) guidelines. The established method demonstrated excellent linearity (R2> 0.99) and sensitivity for all the nitrosamines. Detection and quantification limits were sufficiently low for trace nitrosamine levels having good S/N ratio. The method showed good accuracy in Olmesartan tablet samples, with recoveries ranges between 80 % to 120 %. The new analytical approach has exceptional repeatability and reliability, making it possible to precisely quantify the levels of seven nitrosamines in Olmesartan medoxomil tablets in a single analytical run.

Improved high-performance liquid chromatography tandem mass spectrometry method for quantification of infliximab in pediatric plasma and its application in therapeutic drug monitoring.

The application of infliximab (IFX) to immune-mediated disease is limited by the significant individual variability and associated clinical nonresponse, emphasizing the importance of therapeutic drug monitoring (TDM). Because of the cross-reactivity, limited linear range, and high costs, the clinical application of the previous reported methods was limited. Here, an improved high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to address the issues. This study developed an improved bioanalytical HPLC-MS/MS method coupling nanosurface and molecular-orientation limited proteolysis technology. The commercially available compound P14R was selected as the internal standard. This method was developed with fewer volume of reagents and was thoroughly validated. The validated method was applied to TDM in pediatric inflammatory bowel disease (IBD). Chromatography was performed using a Shim-pack GISS-HP C18 metal-free column (3 μm, 2.1 × 100 mm) with a gradient elution of 0.1% formic acid in water and acetonitrile at 0.4 mL/min. Detection and quantitation were performed using electrospray ionization (ESI) and multiple reaction monitoring in the positive ion mode. The method was validated to demonstrate its selectivity, linearity, accuracy, precision, recovery, matrix effect, and stability. The method exhibited a linear dynamic range of 0.3-100 μg/mL, with intra- and inter-day precision and relative errors below 15%. The recovery and matrix effect were measured as 87.28%-89.72% and 41.98%-67.17%, respectively, which were effectively compensated by the internal standard. A total of 32 samples collected from 24 pediatric patients with IBD were analyzed using the validated method, and only 46.9% achieved the reported targeted trough level. This study developed an improved HPLC-MS/MS method for the quantitative determination of IFX concentration in human plasma. The accurate, reliable, and cost-effective method was validated and utilized in the analysis of clinical samples. The results confirmed the importance of TDM on IFX and the clinical application prospects of the improved method.

Metabolite identification and metabolic pathway analysis of Platycodonis Radix extracts from Tongcheng city in rats

In this study, we delved into the prototypical components and metabolites of Platycodonis Radix extracts(PRE) from Tongcheng city in plasma, urine and feces of rats, and revealed its metabolic pathways and metabolic rules in vivo. The prototypical components and metabolites of PRE in rats were characterized and identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and mass defect filter(MDF). The biological samples were analyzed by ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm), with 0.1% formic acid water(A)-0.1% formic acid acetonitrile(B) as mobile phase, and the biological samples were analyzed in negative ion mode by electrospray ionization mass spectrometry(ESI-MS). Twelve prototypical saponins and twenty-seven metabolites were detected in plasma, urine and feces of rats treated with PRE by oral administration. Eleven prototypical components and nine metabolites were detected in plasma, eleven prototypical components and eight metabo-lites were detected in urine, and ten prototypical components and twenty metabolites were detected in feces. Further studies showed that the metabolic pathways of PRE in rats mainly include oxidation, reduction, acetylation, stepwise hydrolytic deglycosylation, glucuronidation and so on. This study provides a scientific basis for clarifying the pharmacological basis and mechanism of PRE from Tongcheng city.

Simultaneous LC-MS/MS Method for the Quantitation of Probenecid, Albendazole, and Its Metabolites in Human Plasma and Dried Blood Spots

Millions of individuals throughout the world suffer from lymphatic filariasis (LF), which is a morbid disease caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori. These infections belong to tissue-invading nematodes and are one of the major neglected tropical diseases that often result in permanent and enduring disability among individuals in endemic regions. Due to combination therapy, LF eradication has drastically decreased infections globally. The development of blood micro-sampling techniques allowing precise quantitation of drugs in blood would facilitate pharmacokinetic (PK) studies in remote populations. Therefore, an LC-MS/MS bioanalytical method was utilized to analyze albendazole (ABZ), albendazole sulfone (ABZ-ON), albendazole sulfoxide (ABZ-OX), and probenecid (PR) in plasma and dried blood spots. Solid-phase extraction was utilized to extract the analyte from both plasma and blood-spiked DBS. Analytes of interest were eluted with a gradient mobile system using 0.05% formic acid in water (A) and 0.05% formic acid in methanol (B) and separated using a reversed-phase Acquity ®BEH C18 UPLC column (100 × 2.1 mm, 1.7 µm). Precision and accuracy at each QC level were within the acceptable limit, i.e., ±15% for all analytes in both the matrices. Tests for stability under laboratory and storage conditions indicated that no notable changes were observed for plasma and DBS. The LC-MS/MS method demonstrated its capability to consistently identify all target analytes (ABZ, ABZ-ON, ABZ-OX, and PR) at low concentrations, even at the small specimen volumes obtained from DBS cards. This confirms the efficacy and durability of DBS cards as a micro-sampling technique. Moreover, it enhances collection efforts for therapeutic drug monitoring in remote locations for patients infected with lymphatic filariasis.

Study on UPLC–MS/MS Method for Four Compositions of Cangzhu

Background: The legal quality control of Cangzhu is used the single component as an evaluation indicator, which would not be enough to reflect the authenticity of quality. It is necessary to select several typical chemical components as the basis for quality control of medicinal materials and decoction pieces to reflect the content of effective ingredients. Purpose: Based on UPLC-MS/MS, the study aimed to build the content determination method of atractyloidin, atractylidin A, atractylenolide I, and atractylenolide III in Cangzhu from different sources. Materials and Methods: Agilent SB-C18 (2.1 × 100 µm, 1.8 µm) was used to be the stationary phase. The mobile phase system was formed by water-formic acid (1000:1) and acetonitrile-formic acid (1000:1) in gradient elution. The column temperature set at 40℃, and the flow rate was 0.3 mL min–1. Results: The contents of atractyloidin, atractylidin A, atractylenolide I, and atractylenolide III had good linearity in a certain range (r2 ≥ 0. 9990). The RSD of the precision, stability and repetitive test results were less than 3.00%. In addition, the content of the four components were some different among different patches of Cangzhu. Conclusion: The method was simple, rapid and highly sensitive, which was suitable for the determination of atractyloidin, atractylidin A, atractylenolide I, and atractylenolide III in Cangzhu.

Identification and characterization of the rat in-vivo and in-vitro metabolites of tazemetostat using LC-QTOF-MS

In drug discovery, metabolite profiling unveils biotransformation pathways and potential toxicant formation, guiding selection of candidates with optimal pharmacokinetics and safety profiles. Tazemetostat (TAZ) is employed in treating locally advanced or metastatic epithelioid sarcoma. Identification of drug metabolites are of significant importance in improving safety, efficacy and reduced toxicity of drugs. The current study aimed to investigate the comprehensive metabolic fate of TAZ using different in vivo (rat) and in vitro (RLM, HLM, HS9) models. For in vivo studies, drug was orally administered to Sprague–Dawley rats with subsequent analysis of plasma, feces and urine samples. A total of 21 new metabolites were detected across various matrices and were separated on Phenomenex kinetex C18 (2.5 μm; 150 × 4.6 mm) column using acetonitrile and 0.1% formic acid in water as mobile phase. LC-QTOF-MS/MS and NMR techniques were employed to identify and characterize the metabolites from extracted samples. The major metabolic routes found in biotransformation of TAZ were hydroxylation, N-dealkylation, N-oxidation, hydrogenation, hydrolysis and N-acetylation. In silico toxicity revealed potential immunotoxicity for TAZ and few of its metabolites. This research article is the first time to discuss the complete metabolite profiling including identification and characterization of TAZ metabolites as well as its biotransformation mechanism.

A validated LC-MS/MS method for simultaneous quantitation of piperacillin, cefazolin, and cefoxitin in rat plasma and twelve tissues

BackgroundThe investigation of drug disposition in tissues is critical to improving dosing strategy and maximizing treatment effectiveness, yet developing a multi-tissue bioanalytical method could be challenging due to the differences among various matrices. Herein, we developed an LC-MS/MS method tailored for the quantitation of piperacillin (PIP), cefazolin (CFZ), and cefoxitin (CFX) in rat plasma and 12 tissues, accompanied by validation data for each matrix according to the FDA and EMA guidelines. ResultsThe method required only a small sample volume (5 μL plasma or 50–100 μL tissue homogenates) and a relatively simple protocol for simultaneous quantitation of PIP, CFZ, and CFX within different biological matrices. Mobile phase A was composed of 5 mM ammonium formate and 0.1 % formic acid in water, while mobile phase B contained 0.1 % formic acid in acetonitrile. The mobile phase was pumped through a Synergi Fusion-RP column equipped with a guard column with a gradient elution program at a 0.3 mL/min flow rate. The mass spectrometer was operated in positive ionization mode (ESI+) using multiple reaction monitoring. SignificanceThe validated method has been successfully applied to quantify PIP, CFZ, and CFX from the plasma and tissue samples collected in a pilot rat study and will further be used in a large pharmacokinetic study. To our knowledge, this is also the first report presenting long-term, freeze-thaw, and autosampler stability data for PIP, CFZ, and CFX in rat plasma and multiple tissues.

Pharmacokinetics of IMM-H012 in rats using ultra-performance liquid chromatography-tandem mass spectrometry.

The present study examined the pharmacokinetics of IMM-H012 in rat plasma, utilizing ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Internal standard cilostazol was employed, and plasma samples were processed using acetonitrile precipitation. A mobile phase (acetonitrile-0.1% formic acid in water) with gradient elution was used to achieve chromatographic separation using a UPLC BEH C18 column. In multiple reaction monitoring mode, electrospray ionization MS/MS was utilized in positive ionization mode. Based on findings, the lower limit of quantification was 2ng/mL, and the linearity of IMM-H012 in rat plasma was found to be acceptable within the range of 2-2000 ng/mL (R2 > 0.995). The intra-day and inter-day precision relative standard deviation was less than 14% of IMM-H012 in rat plasma. The matrix effect was within the range of 102%-107%, and the accuracy ranged from 92% to 113%. Pharmacokinetics of IMM-H012 in rats after oral administration were successfully studied using UPLC-MS/MS.

Simultaneous quantification of five antiretrovirals in human tissues using ultra-high performance liquid chromatography-tandem mass spectrometry methods for therapeutic drug monitoring at the sites of action

Although antiretroviral therapy (ART) is highly effective for the treatment of HIV-1 infection to suppress virus in the blood, HIV persists in tissues. HIV persistence in the tissues is due to numerous factors, and one of those factors are antiretroviral (ARV) concentrations. ARV concentrations in tissues must be adequate to suppress HIV at the sites of action. While therapeutic drug monitoring in the plasma is well-known, drug monitoring in the tissues provides local assessments of adequate ARV exposure to prevent localized HIV resistance formation. Towards these efforts, we validated an ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) method in human tissues (cervical, rectal, and vaginal tissues) for the simultaneous quantification of five ARVs: bictegravir, cabotegravir, dolutegravir, doravirine, and raltegravir. For this assay, protein precipitation with acetonitrile with stable, isotopically-labeled internal standards followed by supernatant pre-concentration was performed. Analyte separation was accomplished using a multistep UPLC gradient mixture of 0.1 % formic acid in water (A) and acetonitrile (B) with a Waters Cortecs T3 (2.1x100 mm) column. The assay was extensively validated as per the United States Food and Drug Administration Bioanalytical Method Validation Guidance over a clinically observed range (0.05–50 ng/mL) with superb linearity (R2 > 0.99 across all ARVs). The assay run time was 8.5 min. This analytical method achieves appropriate performance of trueness (85.5–107.4 %), repeatability, and precision (CV < 15 %). Our method will be employed for the therapeutic monitoring of guideline-recommended ARVs in human tissues for monitoring therapeutic efficacy in HIV treatment and prevention research efforts.

Characteristics of lipid metabolism after treatment of colon cancer mice with American ginseng vesicles.

Lipid molecules are present in tumours and play an important role in the anti-inflammatory response as well as in antiviral protection. Changes in the type and location of lipids in the intestine following exposure to environmental stressors play an important role in several disorders, including ulcerative colitis (UC), inflammatory bowel disease (IBD), and colorectal cancer. The aim of this work is to provide a new theoretical basis for tumour initiation and development by accurately measuring the spatial distribution of lipids and metabolites in intestinal tissue. Spatial metabolomics allows the detection of samples with minimal sample volume by label-free imaging of complex samples in their original state. The distribution of lipid molecules in tumours has not been reported, although the distribution of lipid molecules in intestinal tissue has been reported in the literature. The range of lipid profiles in colon cancer mouse tumour tissue was compiled using a spatial metabolomics: lipid extraction method. The changes in lipid distribution in two regions after oral administration of American Ginseng (Panax quinquefolius L.) vesicles were also compared. Tumour tissue samples were extracted with 80% methanol-20% formic acid in water. The resulting spatial metabolic profile allowed the identification of seven lipid classes in mouse tumours. The distribution of fibre tissue cells was 23.2% higher than tumour tissue cells, with the exception of the fatty acid (FA) species.

Pharmacokinetic and oral bioavailability study of schaftoside in rats.

A simple and sensitive LC-tandem mass spectrometry method was established and validated for the determination of schaftoside in rat plasma. After prepared by protein precipitation with acetonitrile, schaftoside and internal standard were separated on a Waters HSS T3 column using acetonitrile containing 0.1% formic acid and 0.1% formic acid in water as the mobile phase by gradient elution. The method showed excellent linearity over the range of 0.5-500 ng/mL with acceptable intra- and inter-day precision, accuracy, matrix effect, and recovery. The stability assay indicated that schaftoside was stable during the sample acquisition, preparation, and storage. The method was applied to a pharmacokinetic study of schaftoside in rats. The result suggested that after intravenous administration at a dose of 1 mg/kg, schaftoside was quickly eliminated from the plasma with an elimination half-life of 0.58 h. After oral administration at doses of 5, 10, and 20 mg/kg, schaftoside was quickly absorbed into the plasma and reached the peak concentration (Cmax) of 45.1-104.99 ng/mL at 0.67-1.17 h. The increase of exposure (area under the curve) was linear with the increase of dose. The oral bioavailability was 0.42%-0.71% in the range of 5-20 mg/kg.

Emerging mycotoxin occurrence in chicken feed and eggs from Algeria

Poultry farming has developed into one of Algeria’s most productive industrial farming because of the growing demand for sources of protein among Algerian society. Laying hen feed consists mainly of cereals, which can be contaminated with molds and subsequently with their secondary metabolites known as mycotoxins. These later can pose a serious danger to the production and quality of eggs in the commercial layer industry. This work focuses on the detection of emerging mycotoxins, mainly enniatins (ENNs) and beauvericin (BEA), in poultry feed and eggs from different locations in Algeria. Two different QuEChERS-based extractions were established to extract ENNs and BEA from chicken feed and eggs. The determination of mycotoxin occurrence was achieved by a UHPLC-MS/MS method using 0.1% (v/v) formic acid in water and MeOH as mobile phase, an ESI interface operating in positive mode, and a triple quadrupole mass spectrometer operating in MRM for the detection. Matrix-matched calibration curves were carried out for both matrices, obtaining good linearity (R2 > 0.99). The method performance was assessed in terms of extraction recovery (from 87 to 107%), matrix effect (from − 47 to − 86%), precision (RSD < 15%), and limits of quantitation (≤ 1.1 µg/kg for feed and ≤ 0.8 µg/kg for eggs). The analysis of 10 chicken feed samples and 35 egg samples composed of a 10-egg pool each showed that ENN B1 was the most common mycotoxin (i.e., found in 9 feed samples) with contamination levels ranging from 3.6 to 41.5 µg/kg, while BEA was detected only in one feed sample (12 µg/kg). However, eggs were not found to be contaminated with any mycotoxin at the detection limit levels. Our findings indicate that the searched mycotoxins are present in traces in feed and absent in eggs. This can be explained by the application of a mycotoxin binder. However, this does not put a stop on the conduction of additional research and ultimately setting regulations to prevent the occurrence of emerging mycotoxins.

Determination of vancomycin and meropenem in serum and synovial fluid of patients with prosthetic joint infections using UPLC-MS/MS.

Numerous studies have suggested that intra-articular administration of antibiotics following primary revision surgery may be one of the methods for treating prosthetic joint infection (PJI). Vancomycin and meropenem are the two most commonly used antibiotics for local application. Determining the concentrations of vancomycin and meropenem in the serum and synovial fluid of patients with PJI plays a significant role in further optimizing local medication schemes and effectively eradicating biofilm infections. This study aimed to establish a rapid, sensitive, and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determining the concentrations of vancomycin and meropenem in human serum and synovial fluid. Serum samples were processed using acetonitrile precipitation of proteins and dichloromethane extraction, while synovial fluid samples were diluted before analysis. Chromatographic separation was achieved in 6min on a Waters Acquity UPLC BEH C18 column, with the mobile phase consisting of 0.1% formic acid in water (solvent A) and acetonitrile (solvent B). Quantification was carried out using a Waters XEVO TQD triple quadrupole mass spectrometer with an electrospray ionization (ESI) source in positive ion mode. The multiple reaction monitoring (MRM) mode was employed to detect the following quantifier ion transitions: 717.95-99.97 (norvancomycin), 725.90-100.04 (vancomycin), 384.16-67.99 (meropenem). The method validation conformed to the guidelines of the FDA and the Chinese Pharmacopoeia. The method demonstrated good linearity within the range of 0.5-50 μg/ml for serum and 0.5-100 μg/ml for synovial fluid. Selectivity, intra-day and inter-day precision and accuracy, extraction recovery, matrix effect, and stability validation results all met the required standards. This method has been successfully applied in the pharmacokinetic/pharmacodynamic (PK/PD) studies of patients with PJI.

Isolation and characterization of major degradants in dihydroergotamine injection

AbstractIn this study, we report the systematic approach for characterization of two major degradant impurities, which are not listed in any compendia and were formed during the stability studies of Dihydroergotamine mesylate injection (DHE). An ion-pair UPLC chromatographic method was developed to quantify the related substances present in the DHE injection drug product. The same was used to monitor the impurity profiling during its stability. The two unknown impurities were observed at RRT about 0.08 (Impurity-1) and RRT about 0.80 (Impurity-5) and found to be significantly increasing on stability. Forced degradation studies revealed the nature of the impurity and conditions required for enriching them. A Mass compatible HPLC method was developed to quantify only these two impurities using 25% ammonia and formic acid in water. Their mass numbers were identified using LC MS/MS with triple quadruple mass spectrometer coupled with a HPLC. These two impurities were then isolated from enriched products using preparative HPLC. These impurities were then characterized using Mass and NMR analysis along with Q-TOF elemental analysis.

Codetermination of antimicrobial agents in rabbit tear fluid using LC-MS/MS assay: Insights into ocular pharmacokinetic study.

Managing ocular microbial infections typically requires pharmacotherapy using antibiotic eye drops, such as moxifloxacin hydrochloride (MFX), combined with an antifungal agent like amphotericin B (AB). We carried out and validated an LC-MS/MS assay to quantify these compounds in rabbit tear fluid in order to look into the pharmacokinetics of these two drugs. We employed a protein precipitation technique for the extraction of drugs under examination. A Waters Symmetry C18 column was used to separate the analytes and internal standard. The composition of the mobile phase was like (A) 0.1% v/v formic acid in water and (B) methanol. The detection of MFX and AB was accomplished through the utilization of positive ion electrospray ionization under multiple reaction monitoring mode. The linearity curves for both analytes exhibited an acceptable trendline across a concentration range of 2.34-300 ng/mL for MFX and 7.81-1000 ng/mL for AB in surrogate rabbit tear fluid. The lower limit of quantitation for MFX was 2.34 ng/mL, while for AB, it was 7.81 ng/mL. The approach was strictly validated, encompassing tests of selectivity, linearity (with r2>0.99), precision, accuracy, matrix effects, and stability. Consequently, we employed this method to evaluate the pharmacokinetics profiles of MFX and AB in rabbit tear fluid following single topical doses.

Stability Indicating Method Development and Validation of Glycyrrhizin Using RP-HPLC-DAD: Application to Glycyrrhiza glabra Extract.

Glycyrrhiza glabra is commonly known as licorice. Licorice is the major source of glycyrrhizin. There is no reported stability indicating method for glycyrrhizin in the literature so far. Therefore, it was proposed to develop a stability indicating method and validate the method for glycyrrhizin and its application in G. glabra root extract. Method validation parameters were performed as per the International Council for Harmonization guidelines. The chromatographic separation was achieved on a Zorbax Extended C-18 (250 × 4.6mm, 5μm) column. The separation achieved using the mobile phase consisted of 0.1% formic acid in water and acetonitrile in gradient elution. The flow rate was kept at 1mL/min, and ultraviolet-visible spectroscopy detection was at 250nm. The average retention time of glycyrrhizin was found to be 7.30min. Stress degradation studies were performed and confirmed that only acidic degradation has shown a degradation profile of glycyrrhizin up to 40%. The percentage of glycyrrhizin was found to be 0.40% in the G. glabra extract. This may be further explored for commercial applications.

A comparative study of antioxidant active components in different parts of Artemisia argyi by UPLC-ABTS-Q-TOF-MS

In order to characterize and identify the chemical components in different parts of Artemisia argyi(roots, stems, leaves, and seeds), compounds with antioxidant activity were screened. In this study, ultra-performance liquid chromatography-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt-quadrupole time-of-flight-tandem mass spectrometry(UPLC-ABTS-Q-TOF-MS) was used as an online combination technique. Poroshell 120 SB-Aq(3.0 mm×150 mm, 2.7 μm) was used as the column, and acetonitrile(A)-0.2% formic acid water(B) was adopted as the mobile phase to perform gradient elution and was scanned in positive and negative ion modes. MassLynx software was utilized, and combined with reference substances and related literature, the chemical components of different parts of A. argyi were identified and compared. The antioxidant active components were detected by using the online detection system, and the antioxidant activities of active components of different parts of A. argyi were compared and evaluated by scavenging efficiency. As a result, a total of 87 compounds were identified from extracts of different parts of A. argyi, and 38, 72, 85, and 33 components were identified from roots, stems, leaves, and seeds. 22 compounds with antioxidant activity were screened, and 14, 17, 20, and 11 compounds with antioxidant activity were identified from roots, stems, leaves, and seeds. The results show that there are certain differences in chemical components and antioxidant components of different parts of A. argyi, which provides data support for the resource utilization and further research and development of A. argyi.

Development and Validation of a Rapid and Sensitive LC-APCI-MS/MS Method for the determination of three N-nitrosamine impurities in Varenicline tartrate drug substance and drug products

Nitrosamines impurities may be present in low levels in a variety of products that people are exposed to every day. After thorough investigations, regulatory agencies have outlined that the formation of nitrosamines is possible in the presence of secondary, tertiary, or quaternary amines and nitrite salts under acidic reaction conditions. For safety purpose, all API manufacturers must be developed methods to monitor the low levels of each nitrosamine impurity before the release the individual batches. In this article, we have developed novel, rapid and sensitive liquid chromatography Atmospiric pressure chemical ionization Mass spectroscopy (LC-APCI-MS/MS) method for the determination of N-Nitroso Dimethylamine (NDMA), N-Nitroso Diethylamine (NDEA) and N-Nitroso varenicline impurities in the Varenicline Tartrate drug substance and Drug products. Chromatographic separation is achieved using Inert sustain AQ C18 150 × 4.6mm, 3.0μ column with 0.1% formic acid in water as mobile phase A and 0.1% formic acid in methanol as mobile phase B at the 0.6 mL/min flow rate by using gradient mode of elution upto the 25 minutes total run time. The three impurities are successfully ionized and quantified in positive mode of atmospheric pressure chemical ionization (APCI) using multiple reaction monitoring (MRM). This method was validated according to ICH Q2 (R1) guidelines. The method provided excellent S/N ratios with a high linearity range of 0.66-19.88 ppm with respect to Varenicline Tartrate sample concentrations with a regression coefficient &gt;0.995. The recovery for the method was established with a protocol of three-step sample preparation and was satisfactory within 85-115%. The determined LOQ (0.66 ppm) and LOD (0.22 ppm) values are very low with respect to sample concentration which shows the sensitivity Performance of the method. The method can be routinely applied for the detection of N-nitrosamine impurities (NDMA, NDEA and N-Nitroso varenicline) in Varenicline Tartrate drug substance and Drug products.