Profiling primaquine metabolites in primary human hepatocytes using UHPLC‐QTOF‐MS with 13C stable isotope labeling

Therapeutic efficiency and hemolytic toxicity of primaquine (PQ), the only drug available for radical cure of relapsing vivax malaria are believed to be mediated by its metabolites. However, identification of these metabolites has remained a major challenge apparently due to low quantities and their reactive nature. Drug candidates labeled with stable isotopes afford convenient tools for tracking drug‐derived metabolites in complex matrices by liquid chromatography‐tandem mass spectrometry (LC‐MS‐MS) and filtering for masses with twin peaks attributable to the label. This study was undertaken to identify metabolites of PQ from an in vitro incubation of a 1:1 w/w mixture of ¹³C₆‐PQ/PQ with primary human hepatocytes. Acquity ultra‐performance LC (UHPLC) was integrated with QTOF‐MS to combine the efficiency of separation with high sensitivity, selectivity of detection and accurate mass determination. UHPLC retention time, twin mass peaks with difference of 6 (originating from ¹³C₆‐PQ/PQ), and MS‐MS fragmentation pattern were used for phenotyping. Besides carboxy‐PQ (cPQ), formed by oxidative deamination of PQ to an aldehyde and subsequent oxidation, several other metabolites were identified: including PQ alcohol, predictably generated by oxidative deamination of PQ to an aldehyde and subsequent reduction, its acetate and the alcohol's glucuronide conjugate. Trace amounts of quinone‐imine metabolites of PQ and cPQ were also detected which may be generated by hydroxylation of the PQ/cPQ quinoline ring at the 5‐position and subsequent oxidation. These findings shed additional light on the human hepatic metabolism of PQ, and the method can be applied for identification of reactive PQ metabolites generated in vivo in preclinical and clinical studies. Copyright © 2013 John Wiley & Sons, Ltd.     

Characterization of microholograms recorded in a thermoplastic medium for three-dimensional optical data storage

A three-dimensional optical data storage system that combines a new recording material with a microholographic data format in which data are stored as single-bit microholograms is presented. This format offers less sensitivity to environmental conditions than the page-based holographic approach in addition to an increased compatibility with current storage technologies. The new recording material is based on a thermoplastic material. The results presented indicate that the dimensions of the microholograms are larger than those calculated by use of simple laser beam waist approximations and that multiple layers of microholograms would significantly affect signal levels. Data densities achievable with the microholographic format will likely be limited by those effects.     

Angle-energy distributions of Penning ions in crossed molecular beams. IV. He*(21 S,2 3S)+H2-->He+H2+ +e-

Relative doubly differential cross sections for the Penning ionization of H(2) by spin-state-selected metastable He (1s2s) are reported at center-of-mass collision energies E of 3.1 and 4.2 kcal/mol in a crossed supersonic beam experiment employing a rotatable mass spectrometer detector. The measurements are sufficiently dense in velocity space as to avoid having to functionalize the differential cross sections in order to transform the intensities into the c.m. The H(2) (+) product is scattered sharply forward, c.m. Deltatheta<10 degrees half-width at half-maximum, with respect to the incident direction of H(2) at both energies for both spin states. On the average the products have lost energy upon recoil, mean recoil energy E(')相似文献   

Initial generation and separation of99Mo at Sandia National Laboratories

The radioisotope^99mTc, used in greater than 80% of nuclear medicine applications, has traditionally been produced and supplied to radiopharmaceutical companies in the form of its precursor⁹⁹Mo. Nuclear fission produced⁹⁹Mo had been supplied by Nordion International of Canada and Cintichem, Inc. of New York, USA. With the shutdown of Cintichem's reactor in 1989, a need was recognized for a US supply, and the US Department of Energy recently published a record of decision designating Sandia National Laboratories (SNL) to meet that need. A recent campaign was launched which utilized the SNL Annular Core Research Reactor to irradiate UO₂ coated targets fabricated by Los Alamos National Laboratory to produce⁹⁹Mo. The irradiated targets were chemically processed in the SNL Hot Cell Facility to separate and purify the⁹⁹Mo. The campaign also included final product quality analysis, and process waste handling. The campaign was accomplished with high⁹⁹Mo recovery. Final product quality was assessed at SNL, and samples were sent to an outside laboratory for independent verification. The campaign provided data and experience useful in pursuing US Food and Drug Administration and radiopharmaceutical company approval.     

Accuracy of Gram–Schmidt orthogonalization and Householder transformation for the solution of linear least squares problems

Accuracy of a Gram–Schmidt algorithm for the solution of linear least squares equations is compared with accuracy of least squares subroutines in three highly respected mathematical packages that use Householder transformations. Results from the four programs for 13 test problems were evaluated at 16 digit precision on four different desktop computers using four different compilers. Singular values obtained from the different programs are compared and the effect of pivoting to improve the accuracy is discussed. Solution vectors from the program using the Gram–Schmidt algorithm were generally more accurate or comparable to solution vectors from the programs using the Householder transformations. © 1997 John Wiley & Sons, Ltd.     

Computer extended series solution for unsteady flow in a contracting or expanding pipe

Unsteady flow in a semi-infinite contracting or expanding pipeis reinvestigated using long series analysis. The proposed seriesmethod is useful in analysing the problem for a moderately largeconstant ( = aa/, where a = a(t), the radius of the pipe isa function of time, a(t) is the velocity of the wall, and iskinematic viscosity). For positive values of (expansion ofthe pipe) accuracy of the series representing shear stress andpressure gradient is increased from = 2.89 to = 6.0 by extractingthe singularity followed by completion of the series. For negativevalues of (contraction of the pipe), we revert the series whichresults into the increase of the region of validity of the transposedseries from = -25.0 to = -2.89. Later we use Padé approximantsfor summing them. Also, the asymptotic solution for large valuesof is obtained and it agrees closely with pure numerical valuesof shear stress at the wall and pressure gradient.