A rapid and highly sensitive UPLC-MS-MS method for the quantification of zolpidem tartrate in human EDTA plasma and its application to pharmacokinetic study

A rapid and high sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed and validated for the quantification of zolpidem in human EDTA plasma using ondansetron (IS) as an internal standard. The analyte and IS were extracted from human plasma using ethyl acetate and separated on a C18 column (Inertsil-ODS, 5 μm, 4.6 × 50 mm) interfaced with a triple quadrupole tandem mass spectrometer. The mobile phase, which consisted of a mixture of methanol and 20 mM ammonium formate (pH 5.00 ± 0.05; 75:25 v/v), was injected at a flow rate of 0.40 mL/min. The retention times of zolpidem and IS were approximately 1.76 and 1.22. The LC run time was 3 min. The electrospray ionization source was operated in positive ion mode. Multiple reaction monitoring used the [M + H](+) ions m/z 308.13 → 235.21 for zolpidem and m/z 294.02 → 170.09 for the ondansetron, respectively. Five freeze-thaw cycles was established at -20 and -70°C.The linearity of the response/concentration curve was established in human EDTA plasma over the concentration range 0.10-149.83 ng/mL. The lower detection limit [(signal-to-noise (S/N) > 3] was 0.04 ng/mL and the lower limit of quantification (S/N > 10) was 0.10 ng/mL. This LC-MS-MS method was validated with intra-batch and inter-batch precision of 0.52-8.66.The intra-batch and inter-batch accuracy was 96.66-106.11. Recovery of zolpidem in human plasma was 87.00% and IS recovery was 81.60%. The primary pharmacokinetic parameters were T(max) (h) = (1.25 ± 0.725), C(max) (ng/mL) (127.80 ± 34.081), AUC(0→t), = (665.37 ± 320.982) and AUC(0→∞), 686.03 ± 342.952, respectively.     

Modulation of physical properties of Ter(9,9-ditolylfluorene) by backbone-embedded heteroarenes

[structure: see text] Novel ter(9,9-ditolylfluorene) analogues containing thiophene and pyridine rings embedded as functional constituents within the parent hydrocarbon backbone have been synthesized. These new molecules exhibit highly efficient photoluminescence and high thermal and morphological stability. The electronic structure of the terfluorene backbone is significantly perturbed, which allows modulation of the backbone energy levels.     

An efficient regioselective copper catalyzed multi-component synthesis of 1,3-disubstituted pyrazoles

An efficient synthesis of unsymmetrically substituted 1,3-pyrazole derivatives has been developed via three-component coupling reaction involving 3-(dimethylamino)-1-phenylprop-2-en-1-one, hydrazine, and aryl halides in one pot process exhibiting high regioselectivity. The pyrazole synthesis proceeds via a sequential series of reactions such as Michael addition, heterocyclization, dehydration, and Ullmann cross-coupling.     

Synthesis of tetrahedral diarylheptanoid ent-diospongin A and epimer-diospongin B by employing Julia–Kocienski olefination

Total synthesis of ent-diospongin A and epimer-diospongin B has been accomplished in good yield with high optical purity. The key steps of diospongin synthesis involve Julia–Kocienski olefination, Weinreb amide formation, Grignard reaction, reduction, acetonide deprotection, Lewis acid catalyzed cyclization, and Wacker oxidation.     

Synthesis of Novel Drug‐Like Small Molecules Based on Quinoxaline Containing Amino Substitution at C‐2

A series of novel “drug‐like” small molecules based on quinoxaline containing amino substitution at C‐2 were synthesized. All these molecules were prepared either via the reaction of 2‐phenyl‐3‐(piperazin‐1‐yl)quinoxaline with acyl bromides or benzyl bromides or various carboxylic acids or via the reaction of 2‐chloro‐3‐phenylquinoxaline with various amines. The structures of these novel compounds were confirmed by spectral analysis. The strategy used is simple and efficient and afforded good yields of quinoxaline derivatives.     

Identifying the mechanisms of polymer friction through molecular dynamics simulation

Mechanisms governing the tribological behavior of polymer-on-polymer sliding were investigated by molecular dynamics simulations. Three main mechanisms governing frictional behavior were identified. Interfacial "brushing" of molecular chain ends over one another was observed as the key contribution to frictional forces. With an increase of the sliding speed, fluctuations in frictional forces reduced in both magnitude and periodicity, leading to dynamic frictional behavior. While "brushing" remained prevalent, two additional irreversible mechanisms, "combing" and "chain scission", of molecular chains were observed when the interfaces were significantly diffused.     

A study of room-temperature ferromagnetism in transition metal and fluorine-doped spray-pyrolyzed SnO2 thin films

Room-temperature ferromagnetism has been observed in Co- or Mn-doped SnO₂ and Co- and F-co-doped SnO₂ thin films. A maximum magnetic moment of 0.80μ_B/Co ion has been observed for Sn_0.90Co_0.10O_1.925−δF_0.075 thin films, whereas in the case of Sn_1−xMn_xO_2−δ it was 0.18μ_B/Mn ion for x=0.10. The magnetization of both Sn_1−xCo_xO_2−δ and Sn_1−xCo_xO_2−y−δF_y thin films depends on the free carrier concentration. An anomalous Hall effect has been observed in the case of Co-doped SnO₂ films. However, the same was not observed in the case of Mn-doped SnO₂ thin films. Carrier-mediated interaction is convincingly proved to be the cause of ferromagnetism in the case of Co:SnO₂. It is, however, proposed that no carrier-mediated interaction exists in the case of Mn:SnO₂. Present studies indicate that dopants and hence electronic cloud-lattice interaction plays an important role in inducing ferromagnetism.     

Effects of ambient and humidity exposure on the MgB2 superconductor

Exposure effect of ambient (up to a period of 465 days) and humid atmosphere on stability and the physical properties of bulk samples of MgB₂ has been carried out based on ac-susceptibility and X-ray diffraction measurements performed at different times during the aging. The motivation of this study came from the device application potential of MgB₂ superconductor. It has been observed that on initial exposure to ambient for a period of about 2 months, the MgB₂ samples neither show any sign of phase decomposition nor any significant degradation of superconducting parameters. However, on further exposure to ambient for a period greater than 4 months duration, the samples progressively exhibited the partial conversion of MgB₂ phase into Mg-deficient phases, viz., MgB₆ and MgB₁₂ and also leading to formation of Mg(OH)₂ which is accompanied by decrease in the T_C and poor connectivity of the superconducting grains. When exposed to humid environment for a period of 30 days, a significant degradation was observed in the superconducting properties of MgB₂. In sharp contrast to the case of ambient exposure, the exposure of MgB₂ to humid atmosphere (for 30 days) did not result in any noticeable phase decomposition. A comparison of the magnetically inferred critical current density behavior before and after the humidity exposure of MgB₂ is also presented.     

Naturalness,supersymmetry and implications for LHC and dark matter

It is shown that the Hyperbolic Branch of the radiative electroweak symmetry breaking contains in it three regions: the Focal Point, Focal Curves, and Focal Surfaces. Further, the Focal Point is shown to lie on the boundary of a Focal Curve. These focal regions allow for a small μ while scalar masses can become large and may lie in the several TeV region. It is shown that for the mSUGRA model the current LHC-7 constraint depletes the Focal Point region while regions on Focal Curves and Focal Surfaces remain largely intact. The LHC implications for models which lie on Focal Curves are briefly discussed as well as the implications of dark matter constraints for the Focal Point, Focal Curves and Focal Surfaces are discussed.     

Ion–polymer and ion–ion interaction in PEO‐based polymer electrolytes having complexing salt LiClO4 and/or ionic liquid, [BMIM][PF6]

Ion–polymer and ion–ion association in polymer electrolyte films of PEO complexed with salt LiClO₄, ionic liquid (1‐butyl‐3‐methylimidazolium hexafluorophosphate, BMIMPF₆) and (LiClO₄ + BMIMPF₆) have been studied by laser Raman spectroscopy. The cations (Li⁺ and/or BMIM⁺) of the dopant salt/IL are shown to complex with the ether oxygen of the polymer backbone (i.e. C O C bond of PEO). The polymer–cation complexation results in the appearance of an additional peak at ∼1131 cm⁻¹ apart from the C O C stretching vibrations of PEO at ∼1062 and 1141 cm⁻¹. This peak due to polymer–cation complexation is relatively strong for LiClO₄ than BMIMPF₆, indicating stronger interaction for the former. In the PEO:LiClO₄ and PEO:BMIMPF₆ spectra, Raman peaks at 937 and 747 cm⁻¹, respectively related to Li⁺· ClO and BMIM⁺· PF ‘contact ion pairs’, have also been observed as a result of ion–ion association. In the polymer electrolyte PEO:LiClO₄ + BMIMPF₆ which contained two different anions, viz. ClO and PF, an interesting observation of the formation of ‘cross contact ion pairs’ viz. Li⁺· PF and BMIM⁺· ClO is also reported. Copyright © 2011 John Wiley & Sons, Ltd.