Theoretical investigations on the laser isotope separation of 175Yb for medical applications.

The possibility of laser isotope separation of 175Yb from irradiated natural Yb has been investigated. The optimum process parameters such as powers and bandwidths of the lasers, Doppler broadening and the number density of the atoms have been derived through density matrix calculations. It has been shown that it is possible to produce 175Yb (>42% enriched) at a production rate of 62 µg/hour (or 1.5 mg/day). This corresponds to the production rate of 1350 patient doses (of 7.4 GBq each) per day. The radionuclidic purity of the isotopic mixture is expected to be 99.9999%. The method is highly suitable for the countries having only low-flux nuclear reactors.

Numerical study of the laser isotope separation of optically pumped 102Pd.

The feasibility of laser isotope separation of 102Pd through pulsed laser optical pumping followed by isotope selective photoionization has been studied through density matrix formalism. The effect of various parameters such as bandwidth of the excitation lasers, intensity of the lasers and Doppler broadening of the atomic ensemble on the efficiency of optical pumping and isotope selective photoionization have been evaluated. The optimum number density in the laser-atom interaction region has been derived from the studies of the effect of charge exchange collisions on the degree of enrichment. It has been shown that it is possible to enrich 102Pd up to ~ 23.7% at a production rate of 1.1 mg /h. The achievable degree of enrichment through this photoionization scheme is higher than the previously reported laser isotope separation process. The radionuclidic purity of the irradiated enriched mixture has been found to be suitable for medical applications.

Laser isotope separation of 192Ir.

The following two-step isotope selective photoionization process has been studied for the separation of 192Ir isotope from natural Iridium irradiated in a medium flux reactor for 28 days.5d76s2F9/240.0cm-1→247.5871nm5d76s6p40389.83cm-1J=9/2→307.9nmIr+Density matrix formalism has been used for the investigation of laser isotope separation process. Optimum system parameters such as peak power densities of the excitation and ionization lasers, bandwidth of the excitation laser, angular divergence limit to the atomic ensemble have been derived. Effects of number density and ion travel distance prior to collection on charge exchange probability have also been studied. It has been shown that it is possible produce ∼98% enriched 192Ir at rate of 82 µg/h (27.9 GBq/h or 0.76 Ci/h) which can provide activity of 334 TBq/g or 9027 Ci/g. The enriched 192Ir can be used in both high-dose brachytherapy and high speed radiography. This is the first ever study on the laser based enrichment of Iridium isotopes.

Laser isotope separation of 223Ra.

A three-step photoionization has been theoretically studied for the laser isotope separation of 223Ra through the following photoionization scheme. [Formula: see text] The effect of bandwidth, peak power density of the excitation and ionization lasers, Doppler broadening of the atomic ensemble, number density of the atoms, and charge exchange collisions on the laser isotope separation process has been studied. The optimum system parameters for the separation of 223Ra through this photoionization scheme have been derived. The effect of unknown parameters on the degree of enrichment has also been discussed. It has been theoretically shown that it is possible to produce 223Ra isotope with 98.5% radio-isotopic purity at a rate of 0.74 µg/h corresponding to the production rate of 435 patient doses per hour. This is the first ever study on the laser isotope separation of Radium isotopes.

Enrichment of 150Nd for neutrinoless double-beta decay detection.

A 562 nm-627 nm-597 nm three-step resonant photoionization scheme has been studied using the density matrix formalism for the enrichment of 150Nd in weighable quantities for the neutrinoless double-beta decay detection. The effect of bandwidth of the excitation laser and charge exchange collisions, on the production rates and degree of enrichment has also been studied. Optimum conditions for the efficient enrichment of 150Nd isotope have been derived. It has been shown that it might be possible to produce 50 kg of 66% enriched 150Nd isotope in about five months (16 h/day) using the conditions derived through this investigation. This enables to reach the 0νßß decay half-life limit of ≈ 1.8 × 1025 year for the 150Nd isotope.

Laser isotope separation of 176Lu through off-the-shelf lasers.

We propose a novel and simple method for the laser isotope separation of 176Lu a precursor for the production of 177Lu medical isotope. The physics of the laser-atom interaction has been studied through the dynamics of the atomic level populations using the density matrix formalism. It has been shown that a combination of cw excitation lasers and pulsed ionization laser can be used for the laser isotope separation of 176Lu. The optimum conditions for the efficient and selective separation of 176Lu have been derived by studying the time evolution of level population under laser excitation. It has also been shown that, it might be possible to produce ~ 100% enriched 176Lu isotope at a rate of 5 mg/h, which is higher than all previously reported methods so far. The isotope separation process proposed can be easily adopted using off-the-shelf lasers, for similar atomic systems.

Isotope separation of 176Lu a precursor to 177Lu medical isotope using broadband lasers.

A new photoionization scheme accessible by Rhodamine dye lasers is proposed for the isotope separation of 176Lu.[Formula: see text][Formula: see text] Optimum conditions for the laser isotope separation have been theoretically computed and compared with the previously reported work. The enrichment of ~ 63% can be obtained with > 22 mg/h production rate even when broadband lasers with bandwidth of 500 MHz are employed for the two step excitation. The simplified system requirements for the photoionization scheme combined with a high production rate of 176Lu than previously reported is expected to reduce the global shortage of 176Lu isotope for medical applications.

Estimation of enantiomeric impurity in piperidin-3-amine by chiral HPLC with precolumn derivatization.

A simple, precise, accurate, robust chiral high-performance liquid chromatographic (chiral HPLC) method was developed for estimation of (S)-piperidin-3-amine (S-isomer) in (R)-piperidin-3-amine dihydrochloride (R-AMP). As AMP is a high-melting solid and nonchromophoric compound, development of a suitable chiral method is a challenging task. The proposed chiral HPLC-UV method involves a precolumn derivatization technique with para toluene sulphonyl chloride (PTSC) in the presence of a base to introduce chromophore into analytes. It utilizes chiralpak AD-H column with a simple mobile phase of 0.1% diethyl amine in ethanol with a 0.5 mL/min flow rate. Analytes were monitored by using a UV detector at 228 nm. The resolution between the two enantiomers was more than 4.0. The developed method was validated as per current International Conference on Harmonization (ICH) guidelines.

A novel reverse phase stability indicating RP-UPLC method for the quantitative determination of fifteen related substances in Ranolazine drug substance and drug product.

A gradient reverse-phase ultra performance liquid chromatographic (RP-UPLC) method was developed for the quantitative determination of Ranolazine and potential process-related impurities (starting materials, positional isomers, degradants and byproducts) at the level of 0.1 µg mL(-1) to 0.3 µg mL(-1). Fifteen potential impurities were identified in the crude samples during the process development. Tentative structures for all the impurities were assigned based on m/z values from LC-MS/MS analysis. This method can be used for the quality control of both drug substance and drug product. All these impurities were separated with a gradient UPLC method by using a polar embedded Waters Acquity BEH RP18 100 mm × 2.1 mm,1.7 µm column, monobasic sodium buffer, a basic organic modifier and acetonitrile in the mobile phase. Further, this method is also capable of separating a major oxidative degradant Di-N-oxide. Impurities having electron donating groups(+I effect) on the phenyl ring increased the retention by improved п-п interactions. The drug was subjected to the International Conference on Harmonization (ICH)-prescribed hydrolytic, oxidative, photolytic and thermal stress conditions. The performance of the method was validated according to the present ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, ruggedness and robustness.

A stability-indicating ultra-performance liquid chromatographic method for estimation of related substances and degradants in paliperidone active pharmaceutical ingredient and its pharmaceutical dosage forms.

A simple, linear gradient, rapid, precise and stability-indicating analytical method was developed for the estimation of related substances and degradants of paliperidone API and tablets. The chromatographic separations were achieved using an Acquity ultra-performance liquid chromatograph (BEH 100 mm, 2.1 mm, 1.7 µm C-18 column) employing 0.01 M potassium dihydrogen phosphate buffer (pH 2.0) as mobile phase A and acetonitrile-water (9:1) as mobile phase B. A linear gradient (mobile phase A, mobile phase B in the ratio of 84:16) with a 0.45 mL/min flow rate was chosen. All six impurities were eluted within five minutes of run time. The column temperature was maintained at 25 °C and a detector wavelength of 238 nm was employed. Paliperidone was exposed to thermal, photolytic, hydrolytic and oxidative stress conditions. The stressed samples were analyzed by the proposed method. Considerable degradation of the analyte was observed when it was subjected to oxidative conditions and impurity F was found to be the major degradant. Peak homogeneity data of paliperidone obtained by photodiode array (PDA) detection demonstrated the specificity of the method in the presence of degradants. The method was validated with respect to linearity, precision, accuracy, ruggedness, robustness, limit of detection and limit of quantification.

Thermal decomposition studies of riot control agent ω-chloroacetophenone (CN) by pyrolysis-gas chromatography-mass spectrometry.

Pyrolysis-GC/MS system with on-line micro-furnace was used to make rapid evaluation of ω-chloroacetophenone (CN) decomposition under inert thermal atmospheres. The volatile products evolved during pyrolysis were analyzed by thermal gravimetric analysis (TGA) and Py-GC/MS to obtain specific thermogram and pyrogram. Thermal gravimetric analysis results showed that CN undergoes sublimation at 167°C prior to its decomposition at 229°C. Totally 45 degradation products were identified based on mass spectral library matching with the aid of correlation of the values of boiling point (bp) and retention time. A large number of mono-aromatics and polycyclic aromatic hydrocarbons were observed beyond 600°C. In addition to the aromatic hydrocarbons, oxygenated compounds were also observed during the pyrolysis process. The pyrolysis mechanism was proposed based on the determined pyrolysates and their relative abundance with temperature. The investigation results can provide significant information for understanding the thermal behavior of CN and evaluation of the potential influence of the pyrolysates to living being and the environment.

Complete 1H, 13C, 19F and 31P NMR data assignment of CWC-related chemicals N,N-dialkyl-P-alkyl phosphonamidic fluorides.

The complete multinuclear (1)H, (13)C, (31)P and (19)F NMR data of symmetrically substituted amines containing N,N-dialkyl-P-alkyl phosphonamidic fluorides are presented. Assignment was achieved, using various one-and two-dimensional NMR experiments.

Ketoximes to N-substituted thioamides via PSCl3 mediated Beckmann rearrangement.

N-Substituted thioamides were accessed from ketoximes by utilising PSCl3 as a uniquely capable reagent to induce Beckmann rearrangement as well as to capture the intermediate nitrilium ion.

Direct detection of alkylphosphonic acids in environmental matrices by proton coupled phosphorus NMR.

A simple, convenient, and direct one-dimensional (1D) (31)P NMR technique is demonstrated for the detection of alkylphosphonic acids (marker of nerve agents). The results of detection were validated after conducting various in-house exercises. The confidence generated by this study was found very useful in detection of different alkylphosphonic acids spiked in various official interlaboratory proficiency tests conducted by Organisation for the Prohibition of Chemical Weapons (OPCW).

Absolute frequency determination of the 5P3/2-->7S1/2 transition in 87Rb.

We report the absolute frequency of the important 5S(1/2)-->7S(1/2) two-photon transition in (87)Rb. We access the upper state using two dipole-allowed transitions via the intermediate 5P(3/2) state. This allows us to use much lower laser intensities compared to directly driving the two-photon transition, thereby avoiding potential errors due to the AC Stark shift. Collisional shifts are also minimized because the atomic density required is several orders of magnitude smaller. Our values are consistent with earlier frequency-comb measurements.

A novel quantification method of pantaprazole sodium monohydrate in sesquihydrate by thermogravimetric analyzer.

To demonstrate the applicability of thermogravimetric analyzer as a tool for the quantification of pantaprazole sodium monohydrate in sesquihydrate, studies have been conducted. Thermal analysis (DSC, TGA) crystallographic (PXRD) and spectroscopic techniques (FT-IR) were used for the characterization of the polymorphs. Thermogravimetric analysis (TGA) analysis was explored by high-resolution dynamic (Hi-Res-dynamic) and high-resolution modulated (Hi-Res-modulated) test procedures to quantify the hydrate polymorphic mixtures. The two polymorphic forms exhibited significant differences and good resolution in the second derivative thermogram generated by Hi-Res-modulated test procedure. Thus, the TGA with Hi-Res-modulated test procedure was considered for the quantification of monohydrate in sesquihydrate. The calibration plot was constructed from the known mixtures of two polymorphs by plotting the peak area of the second derivative thermogram against the weight percent of monohydrate. Using this novel approach, 1 wt% limit of detection (LOD) was achieved. The polymorphic purity results, obtained by TGA in Hi-Res-modulated test procedure were found to be in good agreement with the results predicted by FT-IR and was comparable with the actual values of the known polymorphic mixtures. The Hi-Res-modulated TGA technique is very simple and easy to perform the analysis.

Molecularly imprinted polymer-based potentiometric sensor for degradation product of chemical warfare agents. Part I. Methylphosphonic acid.

A biomimetic potentiometric sensor for the specific recognition of methylphosphonic acid (MPA), the degradation product of nerve agents sarin, soman, VX, etc., was designed. This involves the preparation of MPA imprinted polymer particles and removal of the template by soxhlet extraction. Subsequently, the leached MIP particles were dispersed in 2-nitrophenyloctyl ether (plasticizer) and embedded in polyvinyl chloride matrix. The sensor responds to MPA in the concentration range 5x10(-8) to 1x10(-4) and 1x10(-3) to 1x10(-1)M with a detection limit of 5x10(-8)M. The selectivity of the sensor has been tested with respect to chemical analogues such as phosphoric acid, sodium dihydrogen phosphate, organophosphorous pesticide and triazine herbicides. The utility of the sensor was tested for field monitoring of MPA in spiked ground water.

Isotope-selective excitation of 41Ca isotope in Doppler-free two-photon continuous-wave excitation: a case study.

Seven schemes are studied theoretically for Doppler-free two-photon excitation of rare (41)Ca isotope using single-mode continuous-wave lasers. The ionization efficiencies and optical selectivities for all the schemes are calculated for various powers of the excitation and ionization lasers and for various focusing conditions of the two lasers. To maximize the ionization efficiencies and the optical selectivities, wavelength-dependent Stark compensation is used. Certain laser wavelengths of the ionization step termed as magic wavelengths are identified for compensating the Stark shift induced by the excitation laser. The effects of the Stark-shift-induced asymmetry and its reversal by selecting the appropriate magic wavelength for the ionization step for various excitation and ionization laser intensities are investigated. The ionization efficiency and optical selectivity for the best scheme after Stark compensation are found to be 8.4 x 10(-4) and approximately 9 x 10(3), respectively.

Plastic antibody for the recognition of chemical warfare agent sulphur mustard.

Molecularly imprinted polymers (MIPs) known as plastic antibodies (PAs) represent a new class of materials possessing high selectivity and affinity for the target molecule. Since their discovery, PAs have attracted considerable interest from bio- and chemical laboratories to pharmaceutical institutes. PAs are becoming an important class of synthetic materials mimicking molecular recognition by natural receptors. In addition, they have been utilized as catalysts, sorbents for solid-phase extraction, stationary phase for liquid chromatography and mimics of enzymes. In this paper, first time we report the preparation and characterization of a PA for the recognition of blistering chemical warfare agent sulphur mustard (SM). The SM imprinted PA exhibited more surface area when compared to the control non-imprinted polymer (NIP). In addition, SEM image showed an ordered nano-pattern for the PA of SM that is entirely different from the image of NIP. The imprinting also enhanced SM rebinding ability to the PA when compared to the NIP with an imprinting efficiency (alpha) of 1.3.

Kinetics of degradation of sulphur mustard on impregnated carbons.

Kinetics of degradation of sulphur mustard (HD) on the surface of NaOH/CrO3/C, NaOH/CrO3/EDA/C and RuCl3/C systems has been examined by using gas chromatography technique by extracting and analyzing the residual HD periodically. The carbons were prepared by impregnating activated carbon with 4% sodium hydroxide plus 3% Cr(VI) as CrO3 with and without 5% ethylene diamine (EDA) and 5% ruthenium chloride by using their aqueous solutions. Obtained carbons were characterized for surface area analysis by BET conventional method. Kinetic plots reveal that the observed reactions are fast at the initial stages, slow at the later stages and progress to a steady state indicating the first order behavior. Effect of moisture on kinetic rate is also observed. In the case of NaOH/CrO3/C system the rate constant is decreased from 13.36 to 5.53 x 10(-2) h(-1) and half life is increased from 5.2 to 12.54 h while moisture content is increased from 1.9% to 11.2%. Whereas, the rate constant of HD degradation reaction is decreased from 10.4 to 4.14 x 10(-2) h(-1) and half life is increased from 6.7 to 16.72 h while moisture content is increased from 2.1% to 10.8% on NaOH/CrO3/EDA/C. Reaction on RuCl3/C system also behaves in the similar manner. Extracted reaction products were characterized by GC/MS and it is found that on NaOH/CrO3/C, HD degrades to hemisulphur mustard, thiodiglycol and 1,4-oxathiane. Whereas, on NaOH/CrO3/EDA/C, HD is degraded to 1,4-thiazane and it is degraded to divinyl sulphone on RuCl3/C. All these investigations reveal that above mentioned carbons can be used in nuclear, biological and chemical (NBC) filtration systems for protection against sulphur mustard.