Validated ultra-performance liquid chromatography tandem mass spectrometry method for the determination of pramipexole in human plasma

A sensitive and high throughput ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS-MS) method has been developed for the determination of pramipexole, a dopamine agonist, in human plasma. Sample preparation involved liquid-liquid extraction of pramipexole and ranitidine as the internal standard (IS) in ethyl acetate from 100 μL human plasma. The chromatographic separation is achieved on a Waters Acquity UPLC BEH C18 (100 mm × 2.1 mm, 1.7 μm) analytical column using an isocratic mobile phase, consisting of 10 mM ammonium formate (pH 7.50)-acetonitrile (15:85, v/v), at a flow-rate of 0.5 mL/min. The precursor → product ion transition for pramipexole (m/z 212.1 → 153.0) and IS (m/z 315.0 → 176.1) were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring (MRM) and positive ion mode. The method was validated over a wide dynamic concentration range of 20-4020 pg/mL. Matrix effect is assessed by post-column infusion experiment and the process efficiency were 91.9% and 85.7% for pramipexole and IS, respectively. The method is rugged and rapid with a total run time of 1.5 min and is applied to a bioequivalence study of 0.25 mg PPX tablet formulation in 30 healthy Indian male subjects under fasting condition.     

Syntheses of New Unsymmetrical 2,5‐Disubstituted‐1,3,4‐oxadiazoles and 1,2,4‐Triazolo[3,4‐b]‐1,3,4‐thiadiazoles Bearing Thieno[2,3‐c]pyrazolo Moiety

New series of (thieno[2,3‐c]pyrazolo‐5‐yl)‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazoles 10a , 10b , 10c and (thieno[2,3‐c]pyrazol‐5‐yl)‐1,3,4‐oxadiazol‐3(2H)‐yl)ethanones 6a , 6b , 6c has been synthesized from thieno[2,3‐c]pyrazole‐5‐carbohydrazide 3 by multistep reaction sequence. (5‐Aryl‐1,3,4‐oxadiazol‐2‐yl)‐1H‐thieno[2,3‐c]pyrazoles 4a , 4b , 4c were also synthesized from thieno[2,3‐c]pyrazole‐5‐carbohydrazide 3 by cyclization with various aromatic carboxylic acids. The hydrazide 3 was obtained by reaction of thieno[2,3‐c]pyrazole‐5‐carboxylate 2 with hydrazine hydrate in good yield, and compound 2 was obtained by the reaction of 5‐chloro‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde 1 and 2‐ethyl thioglycolate in presence of sodium alcoholate in good yield.     

New Synthesis and Reactions of Ethyl 5‐amino‐4‐cyano‐1‐phenyl‐1H‐pyrazole‐3‐carboxylate

Synthesis of ethyl 5‐amino‐4‐cyano‐1‐phenyl‐1H‐pyrazole‐3‐carboxylate 5 has been achieved via abnormal Beckmann rearrangement of o‐chloroaldehyde 1 . Reaction of o‐aminocarbonitrile 5 with concentrated H₂SO₄ furnished expected o‐aminocarboxamide pyrazole 6 . Key intermediates o‐aminocarbonitrile 5 and o‐aminocarboxamide 6 were successfully utilized for the synthesis of pyrazolopyrimidine derivatives. The replacement of Cl in o‐chlorocarbonitrile 3 with secondary amine furnished new synthon 13 , which was further used for the synthesis of polysubstituted heterocycles. The obtained new products were well characterized by IR, ¹H and ¹³C NMR, and mass spectra.     

Spectroscopy of Charge Transfer Complexes of Aniline Blue

Charge transfer (CT) complexes of aniline blue (AB) were prepared with standard organic acceptors such as TCNQ, TCNE, DDQ, and chloranil and studied with UV-VIS-NIR spectra showing σ→π* and π→π* transitions along with free-carrier absorption due to scattering of light particles which has been found involving phonon–photon, electron–photon, and electron–electron scattering. Infrared spectra contain half power beta density due to hopping conduction and an asymmetric band corresponding to A(k) = A₀k exp(?bk) as absorption associated with diffraction of IR light from the crystalline particles.     

Synthesis,characterization and antimicrobial activities of new bis-hydrazonothioxothiazolidinone derivatives

New bis-hydrazonothioxothiazolidinone derivatives based on 2-thioxothiazolidin-4-one were synthesized in good yields using a simplified experimental condition. The structure of synthesized compounds was established with the help of common physico-chemical analysis and various spectroscopic techniques like FT-IR, mass and ¹H NMR. The results of characterizations are in good agreement with the proposed structure of all the synthesized compounds. Further, the antimicrobial (antibacterial and antifungal) activities of all the synthesized derivatives were carried out against various species like Bacillus subtilis, Escherichia coli, Aspergillous niger and Aspergillous flavus by using agar-cup method. The results of antimicrobial screening showed that all the compounds have mild to moderate activity. However, some of the compounds (3a, 3b, 3d, 3e, 3f, 3g, 3i and 3j) have shown better activity than the other.     

FTIR and thermal studies on gel grown neodymium tartrate crystals

The growth of neodymium tartrate crystals was achieved in silica gel by single diffusion method. Optimum conditions were established for the growth of good quality crystals. Fourier transform infrared (FT-IR) spectroscopic study indicates the presence of water molecules and tartrate ligands and suggests that tartrate ions are doubly ionised. The thermal behaviour of the material was studied using thermogravimetry (TG), differential thermal analysis (DTA), derivative thermogravimetry (DTG) and differential scanning calorimetry (DSC). Thermogravimetric analysis support the suggested chemical formula of the grown crystal to be Nd₂(C₄H₄O₆)₃·7H₂O, and the presence of seven water molecules as water of hydration. It is shown that the material is thermally stable up 45 °C beyond which it decomposes through many stages till the formation of neodymium oxide (Nd₂O₃) at 995 °C. The decomposition pattern is reported to be typical of a hydrated metal tartrate.     

Atom-Transfer Cyclization with CuSO(4)/KBH(4): A Formal "Activators Generated by Electron Transfer" Process Also Applicable to Atom-Transfer Polymerization

The 4-exo and 5-exo-trig atom-transfer cyclizations of 1, 8a-e, 9, 12, and 13 can be mediated with as little as 0.05 mol % of Cu(TPMA)SO(4)·5H(2)O in the presence of 2.5 mol % of borohydride salts in 10 min at room temperature in air. This formal "activators generated by electron transfer" (AGET) procedure utilizes a cheap and oxidatively stable copper source (CuSO(4)·5H(2)O) and can be carried out in environmentally benign solvents (EtOH). It is possible to alter the product distribution in the 5-endo radical-polar crossover reactions of 10a,b and 11 by tailoring the amount of borohydride. Cyclization onto alkynes 14 and 15 is also possible in only 20 min. Controlled radical polymerization of styrene, with increased rates over conventional atom-transfer radical polymerization (ATRP), can be carried out in a controlled fashion (Mn, PDI) using either CuBr or CuSO(4)·5H(2)O and Bu(4)NBH(4).     

Polyaniline thin film optical waveguides for integrated optics and VLSI prepared by vacuum evaporation technique

Polyaniline is emerging as an important polymer material which offers challenging opportunities for both fundamental research and new technological applications in waveguides. Metal doped polyaniline has been prepared initially in the form of powder by a solution growth technique. The emeraldine salt with doped metal was also prepared by solution growth technique. This powder was used for vacuum evaporation on optically flat glass substrate. The dark green doped (Fe, Al) polyaniline thin films were prepared by vacuum evaporation technique (10^?4 torr). Deposited waveguide thin films have been characterized structurally, using X‐ray diffraction (XRD), optically etc. Effective refractive index of the thin film waveguide was also calculated theoretically and experimentally. Waveguide parameters, namely refractive index, propagation loss and depth of vacuum deposited polyaniline thin films optical waveguide have been determined. The optical spectra and structure and waveguide parameters of vacuum deposited polyaniline thin films are strongly affected by the type of doping. It is possible to reduce the losses by addition of Fe to the vacuum deposited polyanine thin film and modify the effective refractive index (O_eff) according to particular requirements. Results are compared with the results in the literature. Copyright © 2002 John Wiley & Sons, Ltd.