Validation of a fully automated high throughput liquid chromatographic/tandem mass spectrometric method for roxithromycin quantification in human plasma. Application to a bioequivalence study

A fully automated high-throughput liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed for the determination of roxithromycin in human plasma. The plasma samples were treated by liquid-liquid extraction (LLE) in 2.2 mL 96-deep-well plates. Roxithromycin and the internal standard clarithromycin were extracted from 100 microL of human plasma by LLE, using methyl t-butyl ether as the organic solvent. All liquid transfer steps were performed automatically using robotic liquid handling workstations. After vortexing, centrifugation and freezing, the supernatant organic solvent was evaporated and reconstituted. Sample analysis was performed by reversed-phase LC-MS/MS, with positive ion electrospray ionization, using multiple-reaction monitoring. The method had a very short chromatographic run time of 1.6 min. The calibration curve was linear for the range of concentrations 50.0-20.0x10(3) ng mL(-1). The proposed method was fully validated and it was proven to be selective, accurate, precise, reproducible and suitable for the determination of roxithromycin in human plasma. Therefore, it was applied to the rapid and reliable determination of roxithromycin in a bioequivalence study after per os administration of 300 mg tablet formulations of roxithromycin.     

Dimensionality control of coupled scattering equations using partitioning techniques

A method of variable reduction of the dimensionality of the coupled equations for inelastic scattering is presented, based upon a projection operator P with a restricted range of orbital angular momentum states. For rotational states in the range O?j ?j^* and total angular momentum large, the coupled equations have dimensionality (j^* + 1) ? N ?(j^* + 1)², where the value of N is controlled by the choice of P. This is in contrast to conventional partitioning techniques which utilize further restrictions on the important molecular rotational states. The equations for the P subspace and its complementary Q subspace are decoupled by an approximation on the equation of motion of Qψ_scat. Information about scattering into the Q subspace is retained, within this degree of approximation, and is reintroduced at the end of the computation with little additional labor. The theory is developed in terms of atom-rigid-rotor scattering, although addition of vibrational modes would not in any way interfere with the basic techniques used.     

Structural anisotropy in unstretched and uniaxially stretched poly(p‐phenylene vinylene)

Poly(p‐phenylene vinylene) or PPV is gaining increasing importance because of its superior electroluminescent efficiency and electrical conductivity. The most widely followed synthetic route for PPV involves synthesis of a precursor polymer using a sulfonium monomer salt. Previous studies have proven that the monomer salt which contains cyclic sulfonium groups yields better quality PPV than when the monomer containing dialkyl sulfonium groups is used. The structure of PPV synthesized using cyclic sulfonium precursor has not been as widely reported as that synthesized using dialkyl sulfonium monomer. In the current work, the structure of PPV, synthesized using a cyclic viz. tetrahydrothiophenium monomer salt, has been studied in detail using the wide angle X‐ray diffraction (WAXD) technique. The study reveals that even in the cast (unstretched) form, PPV shows considerable biaxial orientation in the plane of the film. This preferred orientation is found to occur during the casting process and is independent of the solvent used and casting substrate. On stretching these films to a final draw ratio of 7 : 1, this biaxial orientation is transformed into uniaxial orientation with nematic ordering of PPV chains along the stretch direction and PPV chains assuming three preferred orientations in the plane of the film. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 605–614, 1999     

Decomposition results for general polling systems and their applications

In this paper we derive decomposition results for the number of customers in polling systems under arbitrary (dynamic) polling order and service policies. Furthermore, we obtain sharper decomposition results for both the number of customers in the system and the waiting times under static polling policies. Our analysis, which is based on distributional laws, relaxes the Poisson assumption that characterizes the polling systems literature. In particular, we obtain exact decomposition results for systems with either Mixed Generalized Erlang (MGE) arrival processes, or asymptotically exact decomposition results for systems with general renewal arrival processes under heavy traffic conditions. The derived decomposition results can be used to obtain the performance analysis of specific systems. As an example, we evaluate the performance of gated Markovian polling systems operating under heavy traffic conditions. We also provide numerical evidence that our heavy traffic analysis is very accurate even for moderate traffic. This revised version was published online in June 2006 with corrections to the Cover Date.     

Losartan Interactions with 2-Hydroxypropyl-β-CD

Losartan potassium salt (LSR) is a well-known antihypertensive drug with proven beneficial effects on human health. Its formulation with the non-toxic 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) could improve its pharmacological profile. Thus, its molecular interactions are studied using a combination of Differential Scanning Calorimetry (DSC), Nuclear Magnetic Resonance (NMR) and Molecular Dynamics (MD). First, its complexation is shown through Differential Scanning Calorimetry as lyophilization provided distinct thermal properties in comparison to the mixture. The complexation is further proved by utilizing the chemical shift changes in the complexation and T1 values. Furthermore, the reversible favorable complexation was shown by MD calculations. Such physical chemical properties provide evidence that this formulation must be further explored through biological experiments.     

(+ac,−ac)‐trans‐Bis(hinokitiolato)copper(II) and its chloroform disolvate

The complex trans‐bis(hinokitiolato)copper(II) [systematic name: trans‐bis(3‐isopropyl‐7‐oxocyclohepta‐1,3,5‐trienolato)copper(II); abbreviated name: trans‐Cu(hino)₂], [Cu(C₁₀H₁₁O₂)₂], is a biologically active compound. Three polymorphs of this square‐planar monomer, all with (+sp,−sp) isopropyl substituents, have been reported previously. A fourth polymorph containing (+ac,−ac) isopropyl groups and its chloroform disolvate, [Cu(C₁₀H₁₁O₂)₂]·2CHCl₃, both exhibiting nonmerohedral twinning and with all Cu atoms on centers of crystallographic inversion symmetry, are reported here. One of the differences between all of these polymorphs is the relative conformation of the isopropyl groups with respect to the plane of the molecule. Stacking and Cu...olefin π distances ranging from 3.214 (4) to 3.311 (2) Å are observed, and the chloroform solvent molecules participate in bifurcated C—H...O hydrogen bonds [H...O = 2.26–2.40 Å, C...O = 3.123 (5)–3.214 (5) Å, C—H...O = 127–151° and O...H...O = 74°].     

Novel well-defined star homopolymers and star-block copolymers of poly(n-hexyl isocyanate) by anionic polymerization

Anionic polymerization high-vacuum techniques and appropriate multifunctional initiators/additives were employed for the synthesis of novel star structures of poly(n-hexyl isocyanate) (PHIC). A new trifunctional initiator prepared by the reaction of tris(4-isocyanatophenyl)methane with benzyl sodium was used for the synthesis of three-arm star PHIC. Divinyl benzene and the core-first or the arm-first/core-first (in-out) approach were utilized for the synthesis of multiarm star homopolymers, (PHIC)_n, star-block copolymers, (PHIC-b-PI)_n, and miktoarm star copolymers, (PS)_n(PHIC)_n, where PS is polystyrene. The molecular characteristics obtained by size-exclusion chromatography, equipped with refractive index and two-angle light scattering detectors, nuclear magnetic resonance, spectroscopy, and dilute solution viscometry showed that well-defined structures were synthesized in this study. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2387–2399, 2007     

The Polynomial Behavior of Weight Multiplicities for the Affine Kac–Moody Algebras A(1)r

We prove that the multiplicity of an arbitrary dominant weight for an irreducible highest weight representation of the affine Kac–Moody algebra A ⁽¹⁾ _r is a polynomial in the rank r. In the process we show that the degree of this polynomial is less than or equal to the depth of the weight with respect to the highest weight. These results allow weight multiplicity information for small ranks to be transferred to arbitrary ranks.     

Efficient formulations for pricing under attraction demand models

We propose a modeling and optimization framework to cast a broad range of fundamental multi-product pricing problems as tractable convex optimization problems. We consider a retailer offering an assortment of differentiated substitutable products to a population of customers that are price-sensitive. The retailer selects prices to maximize profits, subject to constraints on sales arising from inventory and capacity availability, market share goals, bounds on allowable prices and other considerations. Consumers’ response to price changes is represented by attraction demand models, which subsume the well known multinomial logit (MNL) and multiplicative competitive interaction demand models. Our approach transforms seemingly non-convex pricing problems (both in the objective function and constraints) into convex optimization problems that can be solved efficiently with commercial software. We establish a condition which ensures that the resulting problem is convex, prove that it can be solved in polynomial time under MNL demand, and show computationally that our new formulations reduce the solution time from days to seconds. We also propose an approximation of demand models with multiple overlapping customer segments, and show that it falls within the class of demand models we are able to solve. Such mixed demand models are highly desirable in practice, but yield a pricing problem which appears computationally challenging to solve exactly.     

Mixed magnesium and nickel nitrate hexahydrates: an unexpected restructuring

Single crystals of the congruently melting equimolar mixture of magnesium nitrate hexahydrate and nickel nitrate hexahydrate have been grown. The compound crystallizes in a structure foreign to both components, namely in the monoclinic cobalt nitrate hexahydrate structure. The cations are located at random on the cation sub-lattice of the latter crystalline structure.