Polymeric Sorbent with Controlled Surface Polarity: An Alternate for Solid-Phase Extraction of Nerve Agents and Their Markers from Organic Matrix.

Extraction and identification of lethal nerve agents and their markers in complex organic background have a prime importance from the forensic and verification viewpoint of the Chemical Weapons Convention (CWC). Liquid-liquid extraction with acetonitrile and commercially available solid phase silica cartridges are extensively used for this purpose. Silica cartridges exhibit limited applicability for relatively polar analytes, and acetonitrile extraction shows limited efficacy toward relatively nonpolar analytes. The present study describes the synthesis of polymeric sorbents with tunable surface polarity, their application as a solid-phase extraction (SPE) material against nerve agents and their polar as well as nonpolar markers from nonpolar organic matrices. In comparison with the acetonitrile extraction and commercial silica cartridges, the new sorbent showed better extraction efficiency toward analytes of varying polarity. The extraction parameters were optimized for the proposed method, which included ethyl acetate as an extraction solvent and n-hexane as a washing solvent. Under optimized conditions, method linearity ranged from 0.10 to 10 µg mL-1 ( r2 = 0.9327-0.9988) for organophosphorus esters and 0.05-20 µg mL-1 ( r2 = 0.9976-0.9991) for nerve agents. Limits of detection (S:N = 3:1) in the SIM mode were found in the range of 0.03-0.075 µg mL-1 for organophosphorus esters and 0.015-0.025 µg mL-1 for nerve agents. Limits of quantification (S:N = 10:1) were found in the range of 0.100-0.25 µg mL-1 for organophosphorus esters and 0.05-0.100 µg mL-1 for nerve agents in the SIM mode. The recoveries of the nerve agents and their markers ranged from 90.0 to 98.0% and 75.0 to 95.0% respectively. The repeatability and reproducibility (with relative standard deviations (RSDs) %) for organophosphorus esters were found in the range of 1.35-8.61% and 2.30-9.25% respectively. For nerve agents, the repeatability range from 1.00 to 7.75% and reproducibility were found in the range of 2.17-6.90%.

Method for Derivatization and Detection of Chemical Weapons Convention Related Sulfur Chlorides via Electrophilic Addition with 3-Hexyne.

Sulfur monochloride (S2Cl2) and sulfur dichloride (SCl2) are important precursors of the extremely toxic chemical warfare agent sulfur mustard and classified, respectively, into schedule 3.B.12 and 3.B.13 of the Chemical Weapons Convention (CWC). Hence, their detection and identification is of vital importance for verification of CWC. These chemicals are difficult to detect directly using chromatographic techniques as they decompose and do not elute. Until now, the use of gas chromatographic approaches to follow the derivatized sulfur chlorides is not reported in the literature. The electrophilic addition reaction of sulfur monochloride and sulfur dichloride toward 3-hexyne was explored for the development of a novel derivatization protocol, and the products were subjected to gas chromatography-mass spectrometric (GC-MS) analysis. Among various unsaturated reagents like alkenes and alkynes, symmetrical alkyne 3-hexyne was optimized to be the suitable derivatizing agent for these analytes. Acetonitrile was found to be the suitable solvent for the derivatization reaction. The sample preparation protocol for the identification of these analytes from hexane spiked with petrol matrix was also optimized. Liquid-liquid extraction followed by derivatization was employed for the identification of these analytes from petrol matrix. Under the established conditions, the detection and quantification limits are 2.6 µg/mL, 8.6 µg/mL for S2Cl2 and 2.3 µg/mL, 7.7 µg/mL for SCl2, respectively, in selected ion monitoring (SIM) mode. The calibration curve had a linear relationship with y = 0.022x - 0.331 and r(2) = 0.992 for the working range of 10 to 500 µg/mL for S2Cl2 and y = 0.007x - 0.064 and r(2) = 0.991 for the working range of 10 to 100 µg/mL for SCl2, respectively. The intraday RSDs were between 4.80 to 6.41%, 2.73 to 6.44% and interday RSDs were between 2.20 to 7.25% and 2.34 to 5.95% for S2Cl2 and SCl2, respectively.

Gas chromatography tandem mass spectrometric analysis of alkylphosphonofluoridic acids as verification targets of nerve agents.

Alkylphosphonofluoridic Acids (APFA) are the major thermal degradation products of G- and A-series nerve agents and thus play a vital role in the verification analysis of Chemical Weapons Convention. Present study focuses on the development of sample clean-up, derivatization procedures and gas chromatography tandem mass spectrometric analysis of APFA in aqueous samples. APFA were found to be much more delicate than the corresponding alkylphosphonic acids and thus required subtle optimizations. Retention of analytes on silica and polymer-based anion exchangers followed by elution under alkaline conditions yielded best recoveries. Elution under acidic conditions led to partial or complete degradation of the analytes to alkylphosphonic acids. Silylation reactions, particularly with MTBSTFA were found the best in terms of chromatographic responses and resolution of the derivative peaks. Methylations with diazomethane, which requires acidic reaction media, failed to produce desired yields of the derivatives. Under optimized conditions, the analytes produced the recoveries ranging from 76.9 to 94.5% with RSD ≤9.2%. The best LOD's in the tandem mass spectrometric analysis ranged from 13 to 56 ng/ml. The applicability of the method was tested by spiking the analytes in the retained aqueous samples received for the 52nd proficiency test conducted by the Organization for the Prohibition of Chemical Weapons (OPCW).

µ-PADs for detection of chemical warfare agents.

Conventional methods of detection of chemical warfare agents (CWAs) based on chromogenic reactions are time and solvent intensive. The development of cost, time and solvent effective microfluidic paper based analytical devices (µ-PADs) for the detection of nerve and vesicant agents is described. The detection of analytes was based upon their reactions with rhodamine hydroxamate and para-nitrobenzyl pyridine, producing red and blue colours respectively. Reactions were optimized on the µ-PADs to produce the limits of detection (LODs) as low as 100 µM for sulfur mustard in aqueous samples. Results were quantified with the help of a simple desktop scanner and Photoshop software. Sarin achieved a linear response in the two concentration ranges of 20-100 mM and 100-500 mM, whereas the response of sulfur mustard was found to be linear in the concentration range of 10-75 mM. Results were precise enough to establish the µ-PADs as a valuable tool for security personnel fighting against chemical terrorism.

A high-resolution phosphorus-31 nuclear magnetic resonance (NMR) spectroscopic method for the non-phosphorus markers of chemical warfare agents.

A high-resolution phosphorus-31 nuclear magnetic resonance (NMR) spectroscopic method has been developed for detection, identification and quantification of non-phosphorus markers of toxic nerve agents (soman and V-class), vesicants (HD, HN-2, HN-3), and incapacitating agent (Bz). These analytes were converted to phosphorus-containing derivatives via phosphitylation reaction of their hydroxyl and sulfhydryl functions (using 2-chloro-4,4,5,5-tetramethyl-1,3,2-dioxaphospholane). This was followed by (31)P{(1)H} and (31)P NMR analysis of these derivatives. The chemical shifts (δ) and coupling constants ((3)J(P-H)) of derivatives were used for their specific detection and identification. The method allowed clear distinction between the alcohols and thiols. The lower limits of detection of these analytes were found to be between 12 and 28 µg obtained from 128 transients of (31)P{(1)H} quantitative NMR experiments. Utility of the method was ensured by the detection and identification of triethanolamine present (at an original concentration of 5 µg/mL) in an aqueous sample from 28th OPCW Official Proficiency Tests.

Detection and identification of alkylphosphonic acids by positive electrospray ionization tandem mass spectrometry using a tricationic reagent.

The retrospective detection and identification of degradation products of chemical warfare agents are of immense importance in order to prove their spillage and use. A highly sensitive liquid chromatography/electrospray ionization tandem mass spectrometric (LC/ESI-MS/MS) method--using an imidazolium-based tricationic reagent--was developed for the detection and identification of the anionic degradation products of nerve agents. A commercially available solution of 1,3-imidazolium-bis-(1-hexylbenzylimidazolium) trifluoride (IBHBI) formed adducts with alkylphosphonic acids (APAs), allowing detection of the APAs by positive mode ESI-MS. Tandem mass spectrometry was used for the unambiguous identification of the APAs. Parameters influencing the formation and stability of these adduct during mass spectrometric analysis, such as solvent composition, concentration of IBHBI, effect of pH and interferences by salts, were optimized. The absolute limits of detection (0.1 ng) for achieved for the APAs were better than those previously reported, and linear dynamic ranges of 10-2000 ng mL(-1) were achieved. The method was repeatable with a relative standard deviation ≤7.3%. APAs present in aqueous samples provided by the Organization for the Prohibition of Chemical Weapons during the 22(nd) and 24(th) Official Proficiency tests were detected and identified as IBHBI adducts. The added advantage of this method is that low-mass analytes are detected at higher mass, thus obviating the problem with background noise at low mass.

Dispersive solid-phase extraction for in-sorbent Fourier-transform infrared detection and identification of nerve agent simulants in analysis for verification of chemical weapon convention.

The combination of dispersive solid-phase extraction (DSPE) and Fourier-transform infrared (FTIR) spectroscopy is presented for detection and quantification of markers and simulants of nerve agents. Hydrophilic-lipophilic balance (HLB) sorbent was used for extraction and enrichment of organophosphonates from water. When the extraction efficiency of DSPE was compared with that of conventional solid-phase extraction (SPE), DSPE was more efficient. Extraction conditions such as extraction time, and type and quantity of sorbent material were optimized. In DSPE, extracted analytes are detected and quantified on the sorbent using FTIR as analytical technique. Absorbance in FTIR due to P-O-C stretching was used for detection and quantification. Infrared absorbance of different analytes were compared by determining their molar absorptivities (ε (max)). Quantitative analyses were performed employing modified Beer's law, and relative standard deviations (RSDs) for intraday repeatability and interday reproducibility were found to be in the range 0.30-0.90% and 0.10-0.80% respectively. The limit of detection (LOD) was 5-10 µg mL(-1). The applicability of the method was tested with an unknown sample prepared by mimicking the sample obtained in an international official proficiency test.

Gas chromatography-electron ionization-mass spectrometry analysis of O,O'- dialkyl methylphosphonites for verification analysis of the Chemical Weapons Convention.

Gas chromatography-mass spectrometry (GC-MS) analysis of O,O'-dialkyl methylphosphonites (DAMPs) was carried out with a view to developing a database and understanding the mechanism of fragmentation. DAMPs are included in the list of schedule 2B4 chemicals of the Chemical Weapons Convention. GC-MS analysis of DAMPs and their deuterated analogs revealed that their fragmentations were dominated by α-cleavages, alkenyl radical loss and hydrogen rearrangements. Based on fragment ions of deuterated analogs and density functional theory calculations, the fragmentation routes were rationalized.

Clinical efficacy and safety of Razumab® (CESAR) study: Our experience with the world's first biosimilar Ranibizumab.

Purpose: : The aim of this study was to evaluate the efficacy and safety of Razumab (the biosimilar Ranibizumab by Intas Pharmaceuticals Ltd.) for the treatment of chorioretinal vascular diseases such as diabetic macular edema (DME), choroidal neovascular membrane (CNVM), and macular edema secondary to retinal vein occlusion (RVO). Methods: : We conducted a single-center, retrospective study, including patients with DME, CNVM, and RVO, who had received treatment with Razumab® between October 2018 and September 2019. Primary outcome measures were the changes in corrected distance visual acuity (CDVA) and central foveal thickness (CFT) from baseline to 1 month and 3 months. Secondary outcome measures included intraocular pressure (IOP) at day 1, any signs of ocular inflammation or systemic adverse events during the follow-up. Results: : One hundred and fifty-three eyes of 141 patients were analyzed. The indications included DME in 70 (45.8%) eyes, CNVM in 70 (45.8%) eyes, and RVO in 13 (8.4%) eyes. Mean CDVA improved from baseline (0.62 ± 0.44) to month 1 (0.45 ± 0.42) and maintained till 3 months (0.42 ± 0.44; P < 0.001). Mean CFT showed significant reduction from baseline (405.68 ± 192.422 µm) to month 1 (286.08 ± 118.36 µm) and month 3 (271 ± 104.24 µm; P < 0.001). None of the eyes recorded IOP >20 mmHg on day 1. No evidence of ocular toxicity or systemic adverse event was noted. Conclusion: : Razumab® showed a rapid improvement in CDVA and CFT in most of the eyes with efficacy observed as early as 1 month and maintained till 3 months. The biosimilar Ranibizumab can be a safe and effective low-cost drug for treating macular diseases.

Multiwalled carbon nanotubes as efficient adsorbent for solid-phase extraction of chemical warfare agents and related chemicals from water.

Optimization of extraction and enrichment parameters of chemical warfare agents and their related chemicals from water are presented using multiwalled carbon nanotubes (MWCNTs) as solid-phase extractant. Selected analytes were O,O'-dialkyl alkylphosphonates, nerve agent and mustards. Extraction parameters, including sample volume, nature and volume of washing and eluting solvent, were optimized. Recoveries of analytes were determined by GC-MS and ranged from 81 to 104%. A comparison with C(18), hydrophilic-lipophilic balance and active carbon sorbents demonstrated the superiority of MWCNTs for non-toxic analogues of nerve agents. Optimized conditions involve 40 mg MWCNTs as the sorbent, 5.0 mL water as the washing solvent, 3 mL ethyl acetate as the eluent and sample loading of 10 mL water spiked at 0.1 µg/mL. The limits of detection (LOD) were achieved down to 1 and 0.05 ng/mL in full scan and selected ion-monitoring modes, respectively.

Test-retest characteristic of [18F]MK-6240 quantitative outcomes in cognitively normal adults and subjects with Alzheimer's disease.

[18F]MK-6240 is a selective, high-affinity PET radiotracer for imaging neurofibrillary tangles (NFT) in Alzheimer's disease (AD). Herein, we report test-retest (T-RT) reproducibility of [18F]MK-6240 in AD and healthy volunteers (HV). Twelve subjects with AD and three cognitively normal HV were enrolled in the study and dynamically scanned for 150 min with [18F]MK-6240 under a T-RT protocol. Two radioactivity doses were investigated: 165 ± 3 MBq (n = 6) and 300 ± 40 MBq (n = 9). Serial arterial blood samples were taken for each scan to obtain metabolite-corrected input functions. Following intravenous administration of [18F]MK-6240, the tracer rapidly partitioned into the brain and its heterogenous distribution pattern was consistent with known NFT pathology in AD. In contrast, uptake in HV was low and uniform across the brain parenchyma. Across all subjects, average T-RT variabilities in NFT-rich regions were ∼21%, ∼14% and ∼6% for various quantitative metrics: total distribution volume (VT), binding potential (BPND), and standardized uptake ratio (SUVR90-120), respectively. No significant differences in SUVR T-RT variability were observed between the high and low injected radioactivity groups (5.6% and 6.1%, respectively). This work suggests [18F]MK-6240 has adequate SUVR T-RT characteristics supporting the use of this outcome in future studies.

Gas chromatography-mass spectrometric identification of cyanide using a nucleophilic substitution based derivatization with S-phenyl benzenethiosulfonate.

A novel, simple and efficient analytical method for GC-MS based identification of cyanide has been developed using a single step nucleophilic substitution based derivatization of cyanide in aqueous medium. The nucleophilic substitution reaction of cyanide with S-phenyl benzenethiosulfonate results in the formation of phenyl thiocyanate as a cyanide derivative and it was found that the relative response of the resultant cyanide derivative was much higher than that of the cyanide derivatives resulting from disulfide based derivatizing agents. The sample preparation protocol for the identification of cyanide in aqueous samples was also optimized with the new derivatizing agent. Derivatization followed by liquid-liquid extraction was employed for the preparation of aqueous samples containing cyanide salts. The resultant samples were subjected to GC-MS analysis for the identification of the cyanide derivative. Under optimized conditions, the detection and quantification limits for cyanide aqueous samples were found to be 0.075 µg mL-1 and 0.25 µg mL-1 respectively. The calibration curve had a linear relationship with y = 0.086x - 0.076 and r2 = 0.997 for the working range of 0.25 µg mL-1 to 50 µg mL-1. The intraday RSDs were between 2.24 and 8.17%, and the interday RSDs were between 2.22 and 12.85%. The method can also be successfully employed for the identification of hydrogen cyanide in aqueous medium. The applicability of the present method was demonstrated by analysing a real sample from apple seed extraction.

Assessment of 18F-labeled mitochondrial complex I inhibitors as PET myocardial perfusion imaging agents in rats, rabbits, and primates.

PURPOSE: Myocardial extractions of mitochondria complex I (MC-I) inhibitors were high and well correlated with flow. This study assessed the potential of MC-I inhibitors to be developed as myocardial perfusion imaging (MPI) agents. METHODS: RP1003, RP1004, and RP1005 representing three classes of MC-I inhibitor were synthesized and radio-labeled with (18)F. These agents were evaluated for IC(50) values, tissue biodistribution, and cardiac PET imaging. (18)F-RP1004 was further examined for first-pass extraction and by imaging in non-human primates (NHP) and rats following coronary ligation. RESULTS: RP1003, RP1004, and RP1005 exhibited high MC-I inhibitory activity with IC(50) of 3.7, 16.7, and 14.4 nM. Heart uptakes in rats (percent injected dose per gram tissue) at 15 and 60 min after injection were 3.52 +/- 0.36 and 2.68 +/- 0.20 for (18)F-RP1003, 2.40 +/- 0.21 and 2.67 +/- 0.27 for (18)F-RP1004, and 2.28 +/- 0.12 and 1.81 +/- 0.17 for (18)F-RP1005. The heart to lung and liver uptake ratios were favorable for cardiac imaging with these agents. In isolated perfused rabbit hearts, the uptake of (18)F-RP1004 increased from 0.74 +/- 0.19 to 1.68 +/- 0.39 mL/min/g at flow rates of 1.66 to 5.06 mL/min/g. These values were higher than or similar to that of (99m)Tc-sestamibi. Cardiac imaging with these agents in rats and rabbits allowed visualization of the heart with minimal lung interference and rapid liver activity clearance. Imaging with (18)F-RP1004 also showed clear myocardium and marked liver activity washout in the NHP and clear detection of the perfusion-deficit area associated with left coronary artery ligation in the rat. CONCLUSION: MC-I inhibitors have the potential to be a new class of MPI agent.

Triazine-Based Covalent Organic Framework: A Promising Sorbent for Efficient Elimination of the Hydrocarbon Backgrounds of Organic Sample for GC-MS and 1H NMR Analysis of Chemical Weapons Convention Related Compounds.

The strict monitoring and precise measurements of chemical warfare agents (CWAs) in environmental and other complex samples with high accuracy have great practical significance from the forensic and Chemical Weapons Convention (CWC) verification point of view. Therefore, this study was aimed to develop an efficient extraction and enrichment method for identification and quantification of toxic agents, especially with high sensitivity and multidetection ability in complex samples. It is the first study on solid-phase extraction (SPE) of CWAs and their related compounds from hydrocarbon backgrounds using covalent triazine-based frameworks (CTFs). This nitrogen-rich CTF sorbent has shown an excellent SPE performance toward sample cleanup by selective elimination of hydrocarbon backgrounds and enrich the CWC related analytes in comparison with the conventional and other reported methods. The best enrichment of the analytes was found with the washing solvent (1 mL of n-hexane) and the extraction solvent (1 mL of dichloromethane). Under the optimized conditions, the SPE method had good linearity in the concentration range of 0.050-10.0 µg mL-1 for organophosphorus esters, 0.040-20.0 µg mL-1 for nerve agents, and 0.200-20.0 µg mL-1 for mustards with correlation coefficients ( r2) between 0.9867 and 0.9998 for all analytes. Limits of detection ( S/ N = 3:1) in the SIM mode were found to be in the range of 0.015-0.050 µg mL-1 for organophosphorus esters, 0.010-0.030 µg mL-1 for nerve agents, and 0.050-0.100 µg mL-1 for blister agents. Limits of quantification ( S/ N = 10:1) were found in the range of 0.050-0.200 µg mL-1 for organophosphorus esters, 0.040-0.100 µg mL-1 for nerve agents, and 0.180-0.350 µg mL-1 for blister agents in the SIM mode. The recoveries of all analytes ranged from 87 to 100% with the relative standard deviations ranging from 1 to 8%. This method was also successfully applied for the sample preparation of 1H NMR analysis of sulfur and nitrogen mustards in the presence of hydrocarbon backgrounds. Therefore, this SPE method provides the single sample preparation for both NMR and GC-MS analyses.

Synthesis and biological evaluation of pyridazinone analogues as potential cardiac positron emission tomography tracers.

A series of fluorinated pyridazinone derivatives with IC50 values ranging from 8 to 4000 nM for the mitochondrial complex 1 (MC1) have been prepared. Structure-activity relationship (SAR) assessment indicated preference of the fluorine label to be incorporated on an alkyl side chain rather than directly on the pyridazinone moiety. Tissue distribution studies of a series of analogues ([18F] 22-28) in Sprague-Dawley (SD) rats identified [18F]27 as the most promising radiotracer with high uptake in cardiac tissue (3.41%ID/g; 30 min post injection) in addition to favorable heart to nontarget organ distribution ratios. MicroPET images of SD rats and nonhuman primates after [18F]27 administration allowed easy assessment of the myocardium through 60 min with minimal lung or liver interference.

Mechanism of uptake and retention of F-18 BMS-747158-02 in cardiomyocytes: a novel PET myocardial imaging agent.

BACKGROUND: BMS-747158-02 is a novel fluorine 18-labeled pyridazinone derivative designed for cardiac imaging. The uptake and retention mechanisms of F-18 BMS-747158-02 in cardiac myocytes were studied in vitro, and the biodistribution of F-18 BMS-747158-02 was studied in vivo in mice. METHODS AND RESULTS: Fluorine 19 BMS-747158-01 inhibited mitochondrial complex I (MC-I) in bovine heart submitochondrial particles with an IC(50) of 16.6 +/- 3 nmol/L that was comparable to the reference inhibitors of MC-1, rotenone, pyridaben, and deguelin (IC(50) of 18.2 +/- 6.7 nmol/L, 19.8 +/- 2.6 nmol/L, and 23.1 +/- 1.5 nmol/L, respectively). F-18 BMS-747158-02 had high uptake in monolayers of neonatal rat cardiomyocytes (10.3% +/- 0.7% of incubated drug at 60 minutes) that was inhibited by 200 nmol/L of rotenone (91% +/- 2%) and deguelin (89% +/- 3%). In contrast, an inactive pyridaben analog, P-070 (IC(50) value >4 micromol/L in MC-1 assay), did not inhibit the binding of F-18 BMS-747158-02 in cardiomyocytes. Uptake and washout kinetics for F-18 BMS-747158-02 in rat cardiomyocytes indicated that the time to half-maximal (t((1/2))) uptake was very rapid (approximately 35 seconds), and washout t((1/2)) for efflux of F-18 BMS-747158-02 was greater than 120 minutes. In vivo biodistribution studies in mice showed that F-18 BMS-747158-02 had substantial myocardial uptake (9.5% +/- 0.5% of injected dose per gram) at 60 minutes and heart-to-lung and heart-to-liver ratios of 14.1 +/- 2.5 and 8.3 +/- 0.5, respectively. Positron emission tomography imaging in the mouse allowed clear cardiac visualization and demonstrated sustained myocardial uptake through 55 minutes. CONCLUSIONS: F-18 BMS-747158-02 is a novel positron emission tomography cardiac tracer targeting MC-I in cardiomyocytes with rapid uptake and slow washout. These characteristics allow fast and sustained accumulation in the heart.

BMS-747158-02: a novel PET myocardial perfusion imaging agent.

BACKGROUND: BMS-747158-02 is a fluorine 18-labeled pyridaben derivative designed as a new myocardial perfusion imaging agent for use with positron emission tomography (PET). This study evaluated BMS-747158-02 in animal models of cardiac perfusion and compared it with established single photon emission computed tomography agents. METHODS AND RESULTS: In a rat biodistribution study, BMS-747158-02 (15 microCi) had substantially higher myocardial uptake than technetium 99m sestamibi (100 microCi) at 15 minutes (3.5% +/- 0.3% %ID/g vs 1.9% +/- 0.1% %ID/g) and 120 minutes (3.2% +/- 0.4% of injected dose per gram vs 1.8% +/- 0.0% of injected dose per gram) after intravenous administration. Uptake ratios of heart to lung and liver at 60 minutes were also higher for BMS-747158-02 (12.7 +/- 1.4 and 3.7 +/- 0.2, respectively) than Tc-99m sestamibi (5.9 +/- 0.5 and 2.4 +/- 0.4, respectively). In an isolated rabbit heart model at flow rates of 1.66 to 5.06 mL x min(-1).g(-1) wet left ventricular weight, the net BMS-747158-02 heart uptake increased proportionally (0.93 +/- 0.15 to 2.44 +/- 0.40 mL.min(-1) x g(-1)) and to a greater extent than that of thallium 201 (0.76 +/- 0.02 to 1.11 +/- 0.02 mL x min(-1) x g(-1)) or Tc-99m sestamibi (0.49 +/- 0.03 to 0.77 +/- 0.08 mL x min(-1) x g(-1)). PET imaging with BMS-747158-02 showed a clear and sustained cardiac uptake in rats, rabbits, and nonhuman primates with minimal lung interference and rapid liver clearance. Myocardial perfusion deficit zones created by either permanent left coronary ligation or reperfusion after ligation in rats were both clearly identified on PET cardiac images of BMS-747158-02 and had good agreement with in vitro histology. CONCLUSIONS: BMS-747158-02 exhibited high and sustained cardiac uptake that was proportional to blood flow, and it represents a new class of PET myocardial perfusion imaging agent.

Analysis of chemical warfare agents in organic liquid samples with magnetic dispersive solid phase extraction and gas chromatography mass spectrometry for verification of the chemical weapons convention.

A simple, sensitive and low temperature sample preparation method is developed for detection and identification of Chemical Warfare Agents (CWAs) and scheduled esters in organic liquid using magnetic dispersive solid phase extraction (MDSPE) followed by gas chromatography-mass spectrometry analysis. The method utilizes Iron oxide@Poly(methacrylic acid-co-ethylene glycol dimethacrylate) resin (Fe2O3@Poly(MAA-co-EGDMA)) as sorbent. Variants of these sorbents were prepared by precipitation polymerization of methacrylic acid-co-ethylene glycol dimethacrylate (MAA-co-EGDMA) onto Fe2O3 nanoparticles. Fe2O3@poly(MAA-co-EGDMA) with 20% MAA showed highest recovery of analytes. Extractions were performed with magnetic microspheres by MDSPE. Parameters affecting the extraction efficiency were studied and optimized. Under the optimized conditions, method showed linearity in the range of 0.1-3.0µgmL(-1) (r(2)=0.9966-0.9987). The repeatability and reproducibility (relative standard deviations (RSDs) %) were in the range of 4.5-7.6% and 3.4-6.2% respectively for organophosphorous esters in dodecane. Limits of detection (S/N=3/1) and limit of quantification (S/N=10/1) were found to be in the range of 0.05-0.1µgmL(-1) and 0.1-0.12µgmL(-1) respectively in SIM mode for selected analytes. The method was successfully validated and applied to the extraction and identification of targeted analytes from three different organic liquids i.e. n-hexane, dodecane and silicon oil. Recoveries ranged from 58.7 to 97.3% and 53.8 to 95.5% at 3µgmL(-1) and 1µgmL(-1) spiking concentrations. Detection of diethyl methylphosphonate (DEMP) and O-Ethyl S-2-diisopropylaminoethyl methylphosphonothiolate (VX) in samples provided by the Organization for Prohibition of Chemical Weapons Proficiency Test (OPCW-PT) proved the utility of the developed method for the off-site analysis of CWC relevant chemicals.

Magnetic hydrophilic-lipophilic balance sorbent for efficient extraction of chemical warfare agents from water samples.

Magnetic hydrophilic-lipophilic balance (MHLB) hybrid resin was prepared by precipitation polymerization using N-vinylpyrrolidone (PVP) and divinylbenzene (DVB) as monomers and Fe2O3 nanoparticles as magnetic material. These resins were successfully applied for the extraction of chemical warfare agents (CWAs) and their markers from water samples through magnetic dispersive solid-phase extraction (MDSPE). By varying the ratios of monomers, resin with desired hydrophilic-lipophilic balance was prepared for the extraction of CWAs and related esters of varying polarities. Amongst different composites Fe2O3 nanoparticles coated with 10% PVP+90% DVB exhibited the best recoveries varying between 70.32 and 97.67%. Parameters affecting the extraction efficiencies, such as extraction time, desorption time, nature and volume of desorption solvent, amount of extraction sorbent and the effect of salts on extraction were investigated. Under the optimized conditions, linearity was obtained in the range of 0.5-500 ng mL(-1) with correlation ranging from 0.9911-0.9980. Limits of detection and limits of quantification were 0.5-1.0 and 3.0-5.0 ng mL(-1) respectively with RSDs varying from 4.88-11.32% for markers of CWAs. Finally, the developed MDSPE method was employed for extraction of analytes from water samples of various sources and the OPCW proficiency test samples.