A sensitive and specific method for the determination of total ribavirin in human red blood cells by liquid chromatography-tandem mass spectrometry

A sensitive and specific method using high-performance liquid chromatography (LC)-tandem mass spectrometry (MS) for the analysis of total ribavirin in human red blood cells (RBC) is developed and validated. The method involves the addition of an internal standard and perchloric acid, the conversion of ribavirin phosphorylated metabolites to ribavirin, purification with a solid-phase exchange cartridge, and LC-MS-MS analysis. The MS-MS is selected to monitor m/z 245-113 for ribavirin and m/z 250-113 for [13C]ribavirin using positive electrospray ionization. The calibration curve is linear over a concentration of 100-10,000 ng/mL with a limit of quantitation of 100 ng/mL. Mean interassay accuracy for quality control (QC) at 100, 1000, and 10,000 ng/mL are 101.8%, 99.4%, and 98.8%, respectively. Mean interassay precision (%CV) for QC at 100, 1000, and 10,000 ng/mL are 5.0%, 5.0%, and 2.5%, respectively. Extractibility of total ribavirin from RBC is confirmed with RBC obtained from a [(14)C]ribavirin-dosed monkey. The method is used to determine the free and total ribavirin concentration in human RBC obtained from hepatitis C patients treated with ribavirin.     

Measurement and Identification of (R)- and (S)-6-O-Desmethylnaproxen Enantiomers as Diastereomeric O-Ethoxycarbonyl/(R)-(+)-1-Phenylethylamides in Urine by GC and GC-MS

Enantioseparations of (R)- and (S)-6-O-desmethylnaproxens as O-ethoxycarbonyl/(R)-(+)-1-phenylethylamides and (R)- and (S)-naproxens as (R)-(+)-1-phenylethylamides were achieved by achiral gas chromatography in a single run within 11 min. The characteristic mass spectral patterns facilitated easier peak identification. The method for determinations of (R)-naproxen (1.0 to 50 ng) and (S)-naproxen (100 to 2000 ng) was linear with acceptable repeatability and accuracy. The enantiomeric composition ratios between (R)- and (S)-6-O-desmethylnaproxens and between (R)- and (S)-naproxens in urine sample collected six hours after oral administration of (S)-naproxen tablets were measured to be 2.2 (± 0.2):97.8 (± 0.2) and 2.1 (± 0.1):97.9 (± 0.1), respectively.     

Proton affinities by reactant ion monitoring: Triphenyl group Va compounds

Proton affinities of a series of triphenyl Group Va compounds have been determined by bracketing using reactant ion monitoring: (C₆H₅)₃N = 904 ± 8 kJ mol^?1, (C₆H₅)₃P = 968 ± 5 kJ mol^?1, (C₆H₅)₃As = 904 ± 8 kJ mol^?1 and (C₆H₅)₃Sb = 846 ± 8 kJ mol^?1. The large difference in substituent effect of phenyl for hydrogen between As or P and N may result from overlap of the 2p orbitals of N with the sp² orbitals on the ring carbons and lack of overlap for P or As. Proton affinities of phenylalkylphosphine oxides are essentially the same, 904 ± 8 kJ mol^?1, independent of alkyl group.     

Analysis of organotin compounds by grignard derivatization and gas chromatography-ion trap tandem mass spectrometry

The determination of organotin compounds in water using gas chromatography-tandem mass spectrometry (GC-MS-MS) is described. Several organotin derivatives were synthesized by the reaction of organotin chlorides with Grignard reagents such as methyl-, propyl- and pentylmagnesium halides. After the optimization of the GC-MS-MS conditions, several derivatizations with the Grignard reagents were compared by evaluating the molar responses and volatilities of the derivatives and derivatization yields. As a result, the derivatizing reagent of choice is pentylmagnesium bromide. Calibration curves for the mono-, di- and tributyltins and mono-, di- and triphenyltins with pentylmagnesium bromide were linear in the range of 0.5-100 pg of Sn. The instrumental detection limits of six organotins ranged from 0.20 to 0.35 pg of Sn. The recovery tests from water samples (500 ml) were performed by using sodium diethyldithiocarbamate (DDTC) as a complexing reagent. Except for monophenyltin, the absolute recoveries of organotins from pure water at 200 ng of Sn/l were satisfactory. The recoveries calibrated by surrogate compounds (perdeuterated organotin chlorides) ranged from 71 to 109%. The method detection limits ranged from 0.26 to 0.84 pg of Sn (500-ml sample). This method was applied to the recovery of organotins from river water and seawater. The calibrated recoveries were between 90 and 122%.     

High pressure studies on new chiral compounds exhibiting TGBA phase

Effects of high pressures on phase sequences of the two homologousn=16 andn=18 of the (3-fluoro-4 ((R) or (S)-methylheptyloxy) 4, (4-fluoro benzoyloxy) tolans) series have been studied. Both compounds exhibit the new twisted Smectic A phase called Twist Grain Boundary TGB_A phase. The high pressure experiments were performed by thermobarometric analysis. The order of the transitions (first or second) have been determined in respect to pressure and temperature. The pressure-temperature phase diagrams show that the TGB_A phase is stabilized by increasing pressure; an inducedN ^* phase appears under high pressure for n=18 leading to the observation of TGB_A-N ^*-I triple point.     

Rare earth impurities in high purity lanthanum oxide determined by neutron activation analysis

Individual rare earth impurities in high purity La₂O₃ (99.9%) have been determined by NAA after pre-separation of the matrix (La). The separation is carried out on an anion exchanger (Dowex 1×8) using different mixtures of methanol/nitric acid as eluants. The rare earth elements from Dy to Lu are eluted quantitatively using a 10% 1M HNO₃-90% methanol mixture, while the light rare earths from Ce to Gd are eluted quantitatively using a 10% 0.05M HNO₃-90% methanol mixture. La, which is retained on the column, is eluted using 0.1M HNO₃. The recoveries of the various rare earth elements have been checked using radiotracers and also by spiking the sample with known amount of elements, and the recoveries are found to be quantitative. Results obtained on a typical high purity lanthanum oxide are reported here.     

Photocrosslinking of functionalized rubber. II. Photoinitiated cationic polymerization of epoxidized liquid natural rubber

Low molecular weight epoxidized natural rubber has been crosslinked within seconds by UV irradiation in the presence of a triarylsulfonium salt. The photoinitiated cationic ring-opening polymerization was studied quantitatively by infrared spectroscopy and shown to proceed with surprisingly long kinetic chains in such solid medium. The high conversion (60%) needed for complete insolubilization, together with the presence of tetrahydrofuran structures, argue in favor of an intramolecular polymerization process involving neighboring epoxy groups. The photoinitiator concentration has a strong influence on the rate and extent of the reaction, as well as on the depth of cure profile. Because of an efficient dark process, close to 100% conversion was reached upon storage of the irradiated elastomer at ambient, with a concomitant increase of the gel fraction and the polymer hardness. The grafting of pendent acrylate groups onto the polymer chain leads to a three-fold decrease of the initial rate of polymerization of the epoxide. The photocuring of natural rubber bearing both epoxy and acrylate groups generates a dual polymer network which combines the properties of the two moieties. © 1995 John Wiley & Sons, Inc.     

Accuracy of free energies of hydration for organic molecules from 6-31g*-derived partial charges

Absolute free energies of hydration have been computed for 13 diverse organic molecules using partial charges derived from ab initio 6-31G* wave functions. Both Mulliken charges and charges fit to the electrostatic potential surface (EPS) were considered in conjunction with OPLS Lennard–Jones parameters for the organic molecules and the TIP4P model of water. Monte Carlo simulations with statistical perturbation theory yielded relative free energies of hydration. These were converted to absolute quantities through perturbations to reference molecules for which absolute free energies of hydration had been obtained previously in TIP4P water. The average errors in the computed absolute free energies of hydration are 1.1 kcal/mol for the 6-31G* EPS charges and 4.0 kcal/mol for the Mulliken charges. For the EPS charges, the largest individual errors are under 2 kcal/mol except for acetamide, in which case the error is 3.7 kcal/mol. The hydrogen bonding between the organic solutes and water has also been characterized. © John Wiley & Sons, Inc.     

Electroosmotic flow controllable coating on a capillary surface by a sol-gel process for capillary electrophoresis

A simple coating procedure employing a sol-gel process to modify the inner surface of a bare fused-silica capillary with a positively charged quaternary ammonium group is established. Scanning electron microscopic studies reveal that a smooth coating with 1 to approximately 2 microm thickness can be obtained at optimized coating conditions. With 40 mM citrate as a running electrolyte, the plot of electroosmotic flow (EOF) versus pH shows a unique three-stage EOF pattern from negative to zero and then to positive over a pH range of 2.5 to 7.0. At pH above 5.5, the direction of the EOF is from the anode to the cathode, as is the case in a bare fused-silica capillary, and the electroosmotic mobility increases as the pH increases. However, the direction of the EOF is reversed at pH below 4.0. Over the pH range of 4.0 to 5.5, zero electroosmotic mobility is obtained. Such a three-stage EOF pattern has been used to separate six aromatic acids under suppressed EOF and to separate nitrate and nitrite with the anions migrating in the same direction as the EOF. The positively charged quaternary ammonium group on the coating was also utilized to minimize the adsorption problem during the separation of five basic drugs under suppressed EOF and during the separation of four basic proteins with the cations migrate in the opposite direction as the EOF. Also, the stability and reproducibility of this column are good.