Formic Acid In Water Research Articles

A Simultaneous Extraction/Derivatization Strategy for Quantitation of Vitamin D in Dried Blood Spots Using LC–MS/MS: Application to Biomarker Study in Subjects Tested for SARS-CoV-2

Vitamin D plays a critical role in bone development and maintenance, and in other physiological functions. The quantitation of endogenous levels of individual vitamin D and its metabolites is crucial for assessing several disease state conditions. With cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leading to the coronavirus disease 2019 (COVID-19) pandemic, there are several studies that have associated lower levels of serum vitamin D with severity of infection in COVID-19 patients. In this context, we have developed and validated a robust LC-MS/MS method for simultaneous quantitation of vitamin D and its metabolites in human dried blood spot (DBS) obtained from participants tested for COVID-19. The chromatographic separation for vitamin D and metabolites was performed using an ACE Excel C18 PFP column protected with a C18 guard column (Phenomenex, Torrance, CA, USA). The mobile phase consisted of formic acid in water (0.1% v/v) as mobile phase A and formic acid in methanol (0.1% v/v) as mobile phase B, operated at a flow rate of 0.5 mL/min. Analysis was performed utilizing the LC-MS/MS technique. The method was sensitive with a limit of quantification of 0.78 ng/mL for all analytes, and had a large dynamic range (200 ng/mL) with a total run time of 11 min. The inter- and intraday accuracy and precision values met the acceptance criteria per the US Food and Drug Administration guidelines. Blood concentrations of 25(OH)D3, vitamin D3, 25(OH)D2, and vitamin D2 over a range of 2-195.6, 0.5-121.5, 0.6-54.9, and 0.5-23.9 ng/mL, respectively, were quantified in 909 DBS samples. In summary, our developed LC-MS/MS method may be used for quantification of vitamin D and its metabolites in DBS, and may be applied to investigations of the emerging role of these compounds in various physiological processes.

LC-MS/MS quantitation of non-psychotropic cannabinoid cannabidiol in aqueous humor

Cannabidiol (CBD) is the most abundant non-psychotropic phytocannabinoid isolated from Cannabis sativa. To support preclinical studies of ocular pharmacology of CBD, a bioanalytical method was developed and validated for quantification of CBD in aqueous humor using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Aqueous humor samples were subjected to protein precipitation by acetonitrile, followed by chromatographic separation using reversed phase LC on a Raptor ARC-18 column with mobile phase A: 0.1 % (v/v) formic acid in water (B) 0.1 % formic acid in acetonitrile (B) as eluents. Detection was carried out with a triple quadrupole mass spectrometer with electrospray ionization operated in positive ion mode. Stable-isotope labeled CBD (CBD-d3) was used as internal standard. The total run time was 8 min. Quantification was accomplished within the validated concentration range of 0.5–500 ng/mL for CBD using a 5 µL sample. The lower limit of quantitation was 0.5 ng/mL. Inter- and intra-day precision is 4.737–7.620 % and 3.426–5.830 %, respectively. Inter- and intra-day accuracy ranged between 99.01 % and 100.2 % and 99.85–101.4 % respectively. The extraction recoveries were found to be 66.06 ± 5.146 %. The established method was successfully applied to investigate ocular pharmacokinetics of CBD in mice. Following intraperitoneal (i.p.) administration of 50 mg/kg CBD, its concentration reaches a Cmax of 71.55 ± 36.64 ng/mL in aqueous humor, with a Tmax of 2 h and a half-life of 1.046 h. The AUC was 183.4 ± 49.17 ng * h/mL. The development and validation of this LC-MS/MS method is an important step toward the goal of assessing the aqueous humor concentrations of CBD and correlating the concentrations of this phytocannabinoid with its ocular pharmacologic effects.

A Validated Chiral LC–MS/MS Method for the Enantioselective Determination of (S)-(+)- and (R)-(-)-Ibuprofen in Dog Plasma: Its Application to a Pharmacokinetic Study

The purpose of this study was to develop a method for simultaneously separating ibuprofen enantiomers using electrospray ionization (ESI) liquid chromatography with tandem mass spectrometry (LC-MS/MS). LC-MS/MS was operated with negative ionization and multiple reaction monitoring modes; transitions were monitored at m/z of 205.1 > 160.9 for ibuprofen enantiomers, 208.1 > 163.9 for (S)-(+)-ibuprofen-d3 [internal standard 1 (IS1)], and 253.1 > 208.9 for (S)-(+)-ketoprofen (IS2), respectively. In a one-step liquid-liquid extraction, 10 μL plasma was extracted with ethyl acetate:methyl tertiary-butyl ether of 7:3. Enantiomer chromatographic separation was carried out with an isocratic mobile phase consisting of 0.008% formic acid in water-methanol (v/v) at a flow rate of 0.4 mL/min on a CHIRALCEL® OJ-3R column (150 × 4.6 mm, 3 µm). This method was fully validated for each enantiomer and results were in compliance with the regulatory guidelines of the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety. The validated assay was executed for nonclinical pharmacokinetic studies after oral and intravenous administration of racemic ibuprofen and dexibuprofen in beagle dogs.

Highly Sensitive and Ultrafast Liquid Chromatography-tandem Mass Spectrometry Internal Standard Method for Determination of Alpha-Tocopherol in Serum and Application of Validated Method on Patient Serum Samples in Pakistan.

To optimize and validate a specific, sensitive and fast liquid Chromatography coupled to triple quadrupole Mass Spectrometric (LC-MS / MS) technique for accurate detection of serum α-tocopherol (Vitamin E) levels. An experimental based study. The Clinical and Forensic Toxicology section of Chughtai Lab, Jail Road Lahore, from April to September 2022. Methanol was used to deproteinize serum samples. The chromatographic separation was achieved using an Agilent Infinity-Lab Poroshell 120EC-C18 column, Agilent 6470 LC-MS/MS (equipped with an Electron Spray Ionization source) in gradient elution mode using 0.1% LCMS grade formic acid in water and LCMS-grade methanol as mobile phases. Hexa-deuterated α-tocopherol was employed as internal standard to minimise matrix interferences. The retention time of α-tocopherol was 3.0 ± 0.1 minutes. The linear concentrations obtained were ranged from 0.05-2 mg/dL with ≥0.985% coefficient of linearity. Detection and lower quantification limits determined were 0.025mg/dL and 0.05mg/dL, respectively. Recovery ranged from 96.5 to 99.8% and ionization suppression was -15.2% and -15.9% at high and low concentrations of α-tocopherol in serum. Intra-day and inter-day coefficient variation values were 4.2-4.9% and 5.0-5.9%, respectively. An efficient and reliable tandem mass spectrometric technique for vitamin E analysis in serum was optimized, validated, and applied to 80 patient samples. This method has usefulness in clinical application for the accurate determination of vitamin E without potential matrix interferences. Vitamin E, LC-MS/MS, Tocopherol, Internal standard, Validation.

Development of analysis method of andrographolide from Andrographis paniculata using UPLC-PDA

Andrographis paniculata is an herbaceous plant belonging to the family Acanthaceae dan also known as the “King of Bitters”. It has been utilized as traditional medicines by the local people in India and Southeast Asia. Many studies have been reported regarding the pharmacological activities of A. paniculata and Andrographolide. Currently, in addition to compound isolation and bioactivity assays, validation of analysis method is also required. Validation is used to demonstrate that the method used is appropriate and the results are precise and accurate. The method used needs to be simple, concise, precise, accurate, and widely used. The analysis in this study was carried out using Ultra-Performance Liquid Chromatography because the instrument operates at high pressure. In addition, the system uses fine particles which can reduce column length as well as solvent and time consumption. This study aims to validate analytical methods in determining the contents of andrographolide in an A. paniculata Leaves. The analytical method was validated through a Waters Alliance UPLC System with photodiode array (PDA) detector. The A. paniculata extract and standard solutions of Andrographolide were analyzed using reverse-phase C18 column which was maintained at 40°C. A mobile phase of 0.1% formic acid in acetnotirile and 0.1% formic acid in water was used at flow rate of 0.3 mL/min to achieve gradient elution. The linearity of the andrographolide showed excellent results (R2= 0.9999) in the concentration range of 7.8–250.0 µg/mL. The LOD and LOQ values of andrographolide were 0.068 µg/mL and 0.205 µg/mL, respectively. The intra-day and inter-day relative standard deviation (RSD) and relative error (RE) accuracy values of andrographolide were <±15. The quantitative analysis found that A. paniculata extract contained 12.45 ±0.06 mg/g of Andrographolide. This developed UPLC-PDA method was proven to be precise, specific, sensitive, and accurate for routine quality assessment of raw material of Andrographis paniculata leaves content.

RP-HPLC method for analytical method development and validation of multi-kinase inhibitor

This study was set out to create an RP-HPLC system that is effective, sensitive, picky, precise, accurate and practical. For this, a UV detection technique for detecting Sorafenib tosylate-loaded solid lipid nanoparticles has been developed and validated. To improve the procedure, many parameters were used (pH and Column). The chromatographic separation was carried out using a Shimadzu prominence-i LC-2030C and a C8 short column (5 m 4.6 x 100 mm). With a runtime of 10 minutes, 10 mL injection volume was maintained at 1 mL/min flow rate. The mobile phase used in the study was a mixture of 70:30 methanol:0.1% formic acid in water. The effluent was detected at 261nm using a UV detector. Drug Entrapment Efficiency (DEE) and Drug Loading (DL) for ST from the extracted SLNs matrix were found to be 86.9% and 19%, respectively. The developed analytical method exhibited a linearity range of 1-64g/ml and an R2 value of 0.998. 0.88 g/ml detection limit (LOD) and 1.0 g/ml limit of quantification (LOQ), and 0.88 g/ml detection limit (LOQ). Using ICH Q2(R1) guidelines, the proposed technique was evaluated, and it was shown to be accurate, linear, robust, and specific. Using the devised analytical method, drug release, drug loading, and drug entrapment effectiveness were all studied.

Determination of 3'-Sialyllactose in Edible Bird's Nests and the Effect of Stewing Conditions on the 3'-Sialyllactose Content of Edible Bird's Nest Products.

Sialyllactose is an acidic oligosaccharide that has an immune-protective effect against pathogens and contributes to developing the immune system and intestinal microbes. In this study, a method for the determination of 3'-sialyllactose by high-performance liquid chromatography tandem mass spectrometry was established. The sample was treated with 0.1% formic acid methanol solution, and the gradient elution was performed with 0.05% formic acid water and 0.1% formic acid acetonitrile. The hydrophilic liquid chromatographic column was used for separation. The results showed that the linearity was good in the concentration range of 1~160 μg/L. The limit of detection (LOD) and the limit of quantification (LOQ) of the method were 0.3 μg/kg and 1.0 μg/kg, the recovery range was 91.6%~98.4%, and the relative standard deviation (RSD) was 1.5%~2.2%. This method is fast and sensitive. In addition, the 3'-sialyllactose content in edible bird's nest products produced by different processes was studied. It was found that within the tested range, 3'-sialyllactose in edible bird's nest products increased with the intensity of stewing and increased with the addition of sugar. In short, the results provided a new method for detecting the nutritional value of edible bird's nests, as well as a new direction for improving the nutritional value of edible bird's nest products.

Comparative Pharmacokinetic Investigation on Multiple Active Aminoalcohol-Diterpenoid Alkaloids after Single Oral Administrations of Monomers and Aqueous Extract of Fuzi (Aconiti Lateralis Radix Praeparata) by UFLC-MS/MS.

To further study the aminoalcohol-diterpenoid alkaloids (ADAs) in Fuzi (Aconiti Lateralis Radix Praeparata), a simple and sensitive UFLC-MS/MS method was established and validated for the determination of five ADAs, aconine, mesaconine, hypaconine, deoxyaconine and fuziline, in rat plasma to compare the pharmacokinetic characteristics of pure ADAs and Fuzi decoction. After precipitating protein with methanol, plasma samples were isolated at 0.5 mL/min flow rate on Waters Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 µm). The mobile phase was composed of 0.1% formic acid-water and methanol with gradient elution. Mass spectrometric inspection was conducted on a 5500 UFLC-MS/MS system with an electrospray ionization source in patterns of positive ion and multiple reaction-monitoring (MRM). All calibration curves were proved to have acceptable linearity (r2 > 0.99) in linear ranges. Intra-day and inter-day precision and the accuracy met the requirements. The matrix effects of all analytes were between 85% and 115% of three concentration levels. This method has been under verification for comparative pharmacokinetic research after oral administration between aqueous extract of Fuzi and single pure ADAs. The results demonstrated that there are evident pharmacokinetic discrepancies between them, and administration in the extract form instead of pure form may contribute to higher absorption.

Mo-modified MnOx for the efficient oxidation of high-concentration glucose to formic acid in water

Severe Mo-modified MnOx binary oxide catalysts were synthesized and served as highly active catalysts for the oxidation of glucose to formic acid in water. A maximum formic acid yield of 79% was achieved from glucose (10 g/L) over Mo(1)-MnOx at 160 °C after 90 min of reaction time. Even when the initial glucose concentration was 110 g/L, 54% of formic acid yield could be obtained with Mo(1)-MnOx, which was almost twice the yield obtained with pristine MnOx as the catalyst. Characterization results showed that the low valence Mn (Mn2+ and Mn3+) ions were the active sites and played key roles in the oxidation of glucose to formic acid. The introduction of Mo could increase the content of low valence Mn (Mn2+ and Mn3+) ions and the adsorbed oxygen (Oads) ratio. A mechanism study indicated that arabinose and glyoxylic acid were the dominant intermediates. Various carbohydrates (xylose, fructose, maltose, sucrose, cellobiose) with high initial concentration afforded formic acid yields >45% demonstrating the potential of Mo(1)-MnOx for transforming lignocellulosic biomass to formic acid.

Development of a sensitive LC-APCI-MS/MS method for simultaneous determination of eleven nitrosamines in valsartan and irbesartan with a simple extraction approach

Nitrosamines (NAs) are potent genotoxic agents (GAs) in several animal species, and some are classified as probable or possible human carcinogens by the International Agency for Research on Cancer (IARC). In July 2018, angiotensin II receptor blockers (ARBs) which are used to treat high blood pressure have been recalled owing to contamination with NAs. In this study, a simple and sensitive method for the determination of eleven NAs in a single analysis was developed, using atmospheric pressure chemical ionisation source coupled liquid chromatography tandem mass spectrometer (LC-APCI-MS/MS). By performing the 17 min-run in dynamic multiple reaction monitoring (dMRM) mode, eleven NAs were separated on a Poroshell HPH C18 (4.6 × 150 mm, 2.7 µm) column with gradient elution implementing mobile phase A consisting of 0.2 % formic acid in water and mobile phase B consisting of methanol. The developed analytical method was successfully applied in both active pharmaceutical ingredients (APIs) and finished products (FPs) of valsartan and irbesartan with straightforward and effective extraction procedures. Good linearity with a correlation coefficient (R2) > 0.996 was achieved over the concentration in a range of 0.5–50 ng/mL. The limits of detection (LODs) ranged in 0.001–0.008 ppm and limits of quantitation (LOQs) ranged in 0.008–0.05 ppm of the method fulfilled thresholds of US Food and Drug Administration (US-FDA) and European Medicines Agency (EMA) for testing of GAs in valsartan and irbesartan. The accuracy of the proposed method ranged from 73.1 % to 115.2 % for APIs and the relative standard deviation (RSD %) was ≤11.3 while these validation parameters were in the range of 80.2–128.5 % and ≤ 10.6 for FPs, respectively.

A simple and rapid HPLC-MS/MS method for therapeutic drug monitoring of amikacin in dried matrix spots

Individualized treatment of amikacin under the guidance of therapeutic drug monitoring (TDM) is important to reduce the occurrence of toxicity and improve clinical efficacy. In the present study, we developed and validated a simple and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine the concentration of amikacin in dried matrix spots (DMS) which the matrix is serum. DMS samples were obtained by spotting volumetric blood onto Whatman 903® cards. Samples were punched into 3 mm diameter discs and extracted with 0.2 % formic acid in water. The HILIC column (2.1 mm × 100 mm, 3.0 µm) under gradient elution was applied, and the analysis time was 3 min per injection. The mass spectrometry transitions were m/z 586.3 → 163.0 for amikacin and m/z 591.4 → 163.1 for D5-amikacin. Full validation was conducted for DMS method, and the method was applied for the amikacin TDM and compared with serum method. The linearity was ranged from 0.5 to 100 mg/L. Both within-run and between-run accuracy and precision of DMS ranged from 91.8 % to 109.6 % and 3.6 % to 14.2 %, respectively. The matrix effect was 100.5 %–106.5 % of DMS method. Amikacin remained stable in DMS for at least 6 days at room temperature, 16 days at 4 °C, 86 days at −20 °C and −70 °C. A good agreement between the DMS method and serum method has been shown in Bland-Altman plots and Passing-Bablok regression. All of the results demonstrated that the DMS methods can be a favorable replacement for amikacin TDM.

Simultaneous quantification of thalidomide, lenalidomide and pomadomide in plasma by LC-MS/MS

ObjectiveTo develop a new method for quantitatively analyzing three immunomodulators (thalidomide, lenalidomide and pomadomide) by liquid chromatography tandem mass spectrometry (LC-MS/MS). MethodsUsing thalidomide-d4 as internal standard, the three analytes were separated on Agilent Zorbax SB-C18(2.1 mm × 100 mm, 3.5 μm, Agilent, USA) column and monitored in multiple reactions monitoring mode in Agilent G6460A triple quadrupole mass spectrometer operating in positive ionization mode. The sample was pretreated by protein precipitation using methanol at 3-fold volume to sample. The mobile phase was comprised of 0.1% formic acid in water (phase A) and acetonitrile (phase B) and was delivered in gradient elution program. The flow rate was 0.3 mL/min, and the injection volume was 5 μL. ResultsThe accuracy and stability of the method are within ±15.0%, and the precision is not >15.0%. The recoveries were 85.04% ∼ 119.07%, and the matrix effect was 73.68% ∼ 116.75%. Specificity, linearity, LLOQ, carry-over and dilution were all in line with the requirements of pharmacopeia and guidelines. The peak concentrations of thalidomide, lenalidomide shows huge inter-individual differences. ConclusionsThis newly developed method was sensitive, simple, and robust and can be used in therapeutic drug monitoring of three immunomodulators in multiple myeloma patients.

A sensitive liquid chromatographic-mass spectrometry method for the quantification of vincristine in whole blood collected with volumetric absorptive microsampling

Vincristine is a well-established cytotoxic drug. In paediatric populations blood collection via venipuncture is not always feasible. Volumetric absorptive microsampling (VAMS) is a less invasive method for blood collection. Furthermore, VAMS lacks the haematocrit effect on the recovery known with dried blood spots. Therefore, a liquid chromatography tandem-mass spectrometry method was developed and validated for the quantification of vincristine in whole blood collected with VAMS devices. Sample preparation consisted of solid-liquid extraction with 0.2% formic acid in water and acetonitrile. The final extract was injected on a C18 column (2.0 ×50 mm, 5 µm). Gradient elution was used and quantification was accomplished with a triple quadruple mass spectrometer operating in the positive mode. The validated concentration range was from 1 to 50 ng/mL with an intra- and inter-accuracy and precision of ± 10.3% and ≤ 7.3%, respectively. This method was able to successfully quantify vincristine concentrations in whole blood collected with VAMS from paediatric oncology patients. Vincristine concentrations in whole blood were non-linearly associated with plasma concentrations, which could be described with a saturable binding equilibrium model.

Response surface optimised photocatalytic degradation and quantitation of repurposed COVID-19 antibiotic pollutants in wastewaters; towards greenness and whiteness perspectives

Environmental context The consumption of repurposed antibiotics increased due to the management of COVID-19, which in turn led to their increased presence in wastewater and potential environmental effects. This change has created a greater need for their analysis and treatment in different environmental water. This work presents a safe, low-cost method for analysing and treating water samples to ensure their suitability for human and animal use. Rationale Certain antibiotics have been repurposed for the management of infected COVID-19 cases, because of their possible effect against the virus, and treatment of co-existing bacterial infection. The consumption of these antibiotics leads to their access to sewage, industrial and hospital effluents, then to environmental waters. This creates a need for the routine analysis and treatment of water resources. Methodology Detection and quantitation of three repurposed antibiotics: levofloxacin (LEVO), azithromycin (AZI) and ceftriaxone (CEF) were studied in different water samples using LC-MS/MS methods employing a C18 column and a mobile phase consisting of 80% acetonitrile/20% (0.1% formic acid in water) after solid phase extraction on Oasis HLB Prime cartridges. Real water samples were treated with synthesised graphitic carbon nitride (g-C3N4) to remove the three types of antibiotics from contaminated water under experimental conditions optimised by response surface methodology, using Box–Behnken experimental design. Results The analytical method was validated in the concentration range of 10–5000 ng mL–1 for the three drugs. The removal percentages were found to be 92.55, 98.48 and 99.10% for LEVO, AZI and CEF, respectively, using synthesised g-C3N4. Discussion The analytical method was used for the estimation of the three cited drugs before and after their removal. The method was assessed using ComplexGAPI as a greenness tool and the RGB 12 algorithm as a whiteness model. The method was applied for the analysis and treatment of real water samples before and after their treatment. It proved to be simple, low-cost and environmentally sustainable.

PHYTOCHEMICALS ANALYSIS AND CYTOTOXIC ACTIVITY OF Lansium domesticum Corr EXTRACT-CISPLATIN COMBINATION AGAINST PANC-1 CELL LINE

The use of chemotherapy such as cisplatin in treating cancer alone can cause many problems, including side effects and resistance. Therefore, currently, efforts are being made to combine cisplatin with natural ingredients such as ethanol extract from duku leaves. Then extracted using ethanol as a solvent. The secondary metabolites of the extract were identified using LC-MS/MS with mobile phase A (0.1 percent formic acid in water) and phase B (0.1 percent formic acid in acetonitrile). The extract and cisplatin were determined by their IC50 values as the basis for carrying out the combination test using the MTT method. All data obtained were processed with Microsoft Excel and analyzed with SPSS 23. The ethanol extract of duku leaves contains about 15 compounds that cannot be clearly identified because they are not listed in the LC-MS/MS library used. Interestingly, there were 5 compounds that gave a sufficiently large absorption each at a retention time of 1.08; 5.18; 9.45; 9.57; 10.70; and 10.82. Cisplatin has stronger cytotoxic properties than the extract with IC50 values of 3.02±0.05 µg/mL and 28.61±0.13 µg/mL, respectively. The combination of these two substances is synergistic with a combination index <1. the combination of extract and cisplatin at doses of 1.75:0.75 and 1.75:0.375 had very strong synergy with a combination index of 0.01 (p>0.05). However, the mechanism of action of this combination is not yet known clearly, so further research is needed on it.

Rapid identification of components in Wuzhuyu Decoction using UHPLC Q-Exactive Orbitrap MS~n and molecular network technology

Wuzhuyu Decoction, the classical formula recorded in the Treatise on Febrile Diseases(Shang Han Lun), has been included in the Catalogue of Ancient Classic Prescriptions(the First Batch). Consisting of Euodiae Fructus, Ginseng Radix et Rhizoma, Zingiberis Rhizoma Recens, and Jujubae Fructus, it is effective in warming the middle, tonifying deficiency, dispelling cold, and descending adverse Qi, and is widely applied clinically with remarkable efficacies. For a classical formula, the chemical composition is the material basis and an important premise for quantity value transfer. This study aimed to establish a rapid identification method of chemical components in Wuzhuyu Decoction by high-resolution mass spectrometry(HR-MS) and molecular network. AQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) was used for sample separation, and acetonitrile-0.1% formic acid in water was used as mobile phases for gradient elution. Q-Exactive Orbitrap MS data were collected in positive and negative ion modes, and GNPS molecular network was plotted according to the similarity of MS/MS fragmentation modes. Cytoscape 3.6.1 was used to screen molecular clusters with similar structures. Finally, the chemical components of Wuzhuyu Decoction were rapidly identified according to the controls, as well as the information of retention time, accurate relative molecular weight of HR-MS, and MS/MS multistage fragments. A total of 105 chemical components were identified in Wuzhuyu Decoction. This study can provide data for the follow-up quality control, standard substance research, and pharmacodynamic material research on Wuzhuyu Decoction, as well as references for the rapid qualitative analysis of the chemical components of Chinese medicine.

A CoPd nanoalloy embedded N-doped porous carbon catalyst for the selective reduction and reductive amination of levulinic acid using formic acid in water

Formic acid-mediated levulinic acid valorization was conducted using a CoPd nanoalloy embedded N-doped carbon catalyst for the production of γ-valerolactone and pyrrolidones.

Determination of licit and illicit drugs and metabolites in human sweat by liquid chromatography-tandem mass spectrometry.

A liquid chromatography-tandem mass spectrometry screening method in sweat was developed for the simultaneous determination of three licit drugs (nicotine, paracetamol, and caffeine); four illicit drugs (cocaine, ketamine, 25I-NBOMe and methamphetamine) and two metabolites (benzoylecgonine and cotinine). Target drugs were liberated from sweat patches with pH 5 sodium acetate buffer and further purified by solid phase extraction (SPE) utilising Strata-X-Drug B cartridges. Optimal solvent constituents for SPE organic wash and elution were 70% v/v methanol in deionised water and 5% v/v ammonium hydroxide in methanol respectively. Chromatographic separation was achieved using a superficially porous particle C18 column with gradient elution, using (A) 0.1% formic acid in water and (B) acetonitrile as mobile phase constituents. Target drugs were identified using a combination of retention time, and the ion ratios for two precursor-product ion transitions for each analyte monitored in multiple reaction monitoring (MRM) mode. The method was linear for all target drugs from 1.0-150.0 ng mL-1 with corresponding limits of quantitation of 1.0 ng mL-1. Limits of detection were found to range from 0.1-0.6 ng per patch. The method was subsequently applied to the analysis of sweat samples from five male and four female participants aged 20-25 years. Sweat was collected from two areas (right forearm and left thigh) using protected layers of gauze. All eighteen patches tested positive for at least one target analyte. The results of this study not only show a multi-substance screening method was achieved but also that sweat patches can be used to indicate an individual's drug use. Therefore, they can provide an alternative non-invasive technique for forensic applications.

Development of a New Method for Simultaneous Quantitation of Plasma Concentrations of Voriconazole and Voriconazole N-Oxide Using Column-Switching LC-MS/MS and Its Application in Therapeutic Drug Monitoring.

Voriconazole therapy for fungal infections usually continues for several years and is often administered on an outpatient basis. Maintaining the voriconazole plasma concentration in the therapeutic range is highly important for effective therapy; however, it is difficult to obtain sufficient information to assess the voriconazole concentration in outpatients. Therefore, we developed a method to simultaneously measure the plasma concentrations of voriconazole and its major metabolite, voriconazole N-oxide, to obtain rapid results after outpatient blood collection and before medical consultation and to attain a better understanding of adherence and the drug-drug interactions of voriconazole. Fifty microliters of patient plasma was deproteinized with methanol, injected into the liquid chromatography-tandem mass spectrometry system, and purified using an online column. Separation was achieved on an InertSustain C18 column (2.1 mm id × 50 mm, 2 μm) with a mobile phase of 30:70 (0.1% formic acid in water:methanol) at a flow rate of 0.2 mL/min. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode. The analysis time was 4 min. The calibration curve was linear, in the range of 0.1 μg/mL to 20 μg/mL for voriconazole and 0.05 μg/mL to 10 μg/mL for voriconazole N-oxide, with a coefficient of determination at R2 > 0.999. There is no need to dilute the patient's plasma even if the concentration of voriconazole is near the upper limit of measurement. Furthermore, the short measurement-time could immediately inform physicians of the patient's voriconazole concentration during ambulatory medical care. Simultaneous measurement of voriconazole and voriconazole N-oxide may also be useful for the immediate adjustment of voriconazole dosage in outpatients and would help us to understand adherence or drug-drug interactions in plasma voriconazole concentrations.

Evaluation on the Metabolic Activity of Two Carboxylesterase Isozymes in Mouse Liver Microsomes by a LC-MS/MS Method.

An applicable method for the precise measurement of major carboxylesterase (CESs) activity in liver still limited. Clopidogrel and irinotecan are specific substrates for CES1 and CES2, respectively. Clopidogrel is metabolized to the inactive metabolite clopidogrel carboxylate (CCAM) by CES1. Irinotecan is metabolized to the active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) by CES2. In the present study, the LC-MS/MS method for the determination of CCAM and SN-38 were separately developed to characterize the metabolic activities of CES1 and CES2 in mouse liver microsomal. CCAM was separated on a Ecosil ODS column with an isocratic mobile phase consisted of 5mmol/L ammonium formate and 0.1% formic acid in water and acetonitrile (15:85, V:V) at a flow rate of 0.4mL/min. SN-38 was separated on a Waters symmetry C18 column with an gradient mobile phase consisted of 5mmol/L ammonium formate and 0.1% formic acid in water and acetonitrile at a flow rate of 0.3mL/min. Calibration curves were linear within the concentration range of 100-20,000ng/mL for CCAM and 1-200ng/mL for SN-38. The results of method showed excellent accuracy and precision. The recovery rate, matrix effect and stability inspection results were within the acceptance criteria. The optimized incubation conditions were as follows: protein concentration of microsomes were all 0.1mg/mL, incubation time was 60min for clopidogrel and 30min for irinotecan, respectively. This method was sensitive and applicable for the determination of the activity of CESs in the mouse liver microsomes.