Highly sensitive method for the determination of ropinirole with a lower limit of quantitation of 3.45 pg/mL in human plasma by LC‐ESI‐MS/MS: application to a clinical pharmacokinetic study

A highly sensitive, rapid assay method has been developed and validated for the estimation of ropinirole (RPR) in human plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive‐ion mode. A solid‐phase process was used to extract RPR and citalopram (internal standard, IS) from human plasma. Chromatographic separation was operated with 0.2% ammonia solution:acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on a Hypurity C₁₈ column with a total run time of 3.2 min. The MS/MS ion transitions monitored were 261.2 → 114.2 for RPR and 325.1 → 209.0 for IS. Method validation and clinical sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 3.45 pg/mL and the linearity was observed from 3.45 to 1200 pg/mL. The intra‐day and inter‐day precisions were in the range of 4.71–7.98 and 6.56–8.31%, respectively. This novel method has been applied to a pharmacokinetic study of RPR in humans. Copyright © 2008 John Wiley & Sons, Ltd.     

Ultratrace analysis of uracil and 5‐fluorouracil by molecularly imprinted polymer brushes grafted to silylated solid‐phase microextraction fiber in combination with complementary molecularly imprinted polymer‐based sensor

Main inborn errors of metabolism diagnosable through uracil (Ura) analysis and the therapeutic monitoring of toxic 5‐fluorouracil (5FU) in dihydro pyrimidine dehydrogenase (DPD) deficient patients require a sensitive, reproducible, selective and accurate method. In this work, an artificial receptor in the format of molecularly imprinted polymer (MIP) brush ‘grafted to’ the surface of sol–gel immobilized on cost‐effective homemade solid‐phase microextraction (SPME) fibers, individually imprinted with either of Ura and 5FU, was used in combination with a voltammetric sensor duly modified with the same MIP. This combination provided up to 10‐ and 8.4‐fold preconcentrations of Ura and 5FU, respectively, which was more than sufficient for achieving stringent detection limits in the primitive diagnosis of uracil disorders and fluoropyrimidine toxicity in DPD‐deficient patients. The proposed method permits the assessment of Ura and 5FU plasma concentrations with detection limits pf 0.0245 and 0.0484 ng mL^?1 (RSD = 1.0–2.5%, S/N = 3), respectively, without any problems of non‐specific false‐positives and cross‐reactivities in complicated matrices of biological samples. Copyright © 2008 John Wiley & Sons, Ltd.     

An implementation of the Spalart–Allmaras DES model in an implicit unstructured hybrid finite volume/element solver for incompressible turbulent flow

In this paper, we describe an implicit hybrid finite volume (FV)/element (FE) incompressible Navier–Stokes solver for turbulent flows based on the Spalart–Allmaras detached eddy simulation (SA‐DES). The hybrid FV/FE solver is based on the segregated pressure correction or projection method. The intermediate velocity field is first obtained by solving the original momentum equations with the matrix‐free implicit cell‐centered FV method. The pressure Poisson equation is solved by the node‐based Galerkin FE method for an auxiliary variable. The auxiliary variable is closely related to the real pressure and is used to update the velocity field and the pressure field. We store the velocity components at cell centers and the auxiliary variable at vertices, making the current solver a staggered‐mesh scheme. The SA‐DES turbulence equation is solved after the velocity and the pressure fields have been updated at the end of each time step. The same matrix‐free FV method as the one used for momentum equations is used to solve the turbulence equation. The turbulence equation provides the eddy viscosity, which is added to the molecular viscosity when solving the momentum equation. In our implementation, we focus on the accuracy, efficiency and robustness of the SA‐DES model in a hybrid flow solver. This paper will address important implementation issues for high‐Reynolds number flows where highly stretched elements are typically used. In addition, some aspects of implementing the SA‐DES model will be described to ensure the robustness of the turbulence model. Several numerical examples including a turbulent flow past a flat plate and a high‐Reynolds number flow around a high angle‐of‐attack NACA0015 airfoil will be presented to demonstrate the accuracy and efficiency of our current implementation. Copyright © 2008 John Wiley & Sons, Ltd.     

Simultaneous LC–MS–MS Analysis of Valsartan and Hydrochlorothiazide in Human Plasma

A rapid and specific liquid chromatographic–tandem mass spectrometric method is described for simultaneous analysis of valsartan (VAL) and hydrochlorothiazide (HCTZ) in human plasma. VAL and HCTZ were chromatographed on a C₈ column with 75:15:10 (v/v) acetonitrile–methanol–0.001% aqueous ammonia as mobile phase. VAL and HCTZ were eluted at 0.69 min and 1.22 min, respectively, and, after electrospray ionization (ESI), detected in selected-reaction-monitoring mode. The precursor to product-ion transitions m/z 434.32 → 179.22 and m/z 295.85 → 204.86 were used to quantify VAL and HCTZ, respectively. Recovery by solid-phase extraction was >90% for both analytes and the internal standard. The method was suitable for application to a pharmacokinetic study after oral administration of tablet containing 160 mg VAL and 25 mg HCTZ to 18 healthy volunteers.     

Quantification of Quetiapine in Human Plasma by LC–MS–MS

A rapid liquid chromatographic method with electrospray ionization tandem mass spectrometric detection has been developed and validated for quantification of quetiapine in heparinized human plasma. Plasma samples, without a drying and reconstitution step, were extracted by solid-phase extraction and eluted with acetonitrile. The analyte and zolpidem tartrate (internal standard, IS) were chromatographed on a C₁₈ column; the mobile phase was 85:15 (v/v) acetonitrile–5 mM ammonium formate, pH adjusted to 4.5 with formic acid, at a flow rate of 0.5 mL min⁻¹. The retention times of quetiapine and the IS were 1.25 and 1.05 min, respectively, and the run time was 1.8 min per sample. Selected reaction monitoring of MH⁺ at m/z 384.12 and 308.11 resulted in stable fragment ions with m/z 253.02 and 235.09 for quetiapine and the IS, respectively. Response was a linear function of concentration in the range 1.0–240.0 ng mL⁻¹, with r ≥ 0.9994. Recovery of quetiapine and the IS ranged from 74.82 to 85.57%. The assay has excellent characteristics and has been successfully used for analysis of quetiapine in healthy human subjects in a bioequivalence study.

     

CtrA gene based electrochemical DNA sensor for detection of meningitis

Electrochemical DNA sensor has been fabricated by immobilizing thiolated single stranded oligonucleotide (ssDNA) probe onto gold (Au) coated glass electrode for meningitis detection using hybridization with complementary DNA (CtrA) in presence of methylene blue (MB). These electrodes (ssDNA/Au and dsDNA/Au) have been characterized using atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR), electrochemical impedance spectroscopy (EIS) and cyclic voltammetric (CV) technique. The DNA/Au electrode can detect the complementary DNA in the range of 7–42 ng/μl in 5 min (hybridization) with response time 60 s and electrode is stable for about 4 months when stored at 4 °C. The sensitivity of dsDNA/Au electrode is 115.8 μA/ng with 0.917 regression coefficient (R).     

Magnetic hyperthermia with biphasic gel of La1−xSrxMnO3 and maghemite

Magnetic hyperthermia experiments were carried out using a biphasic gel of La_1−xSr_xMnO₃(LSMO) and γ-Al_0.07 Fe_1.93O₃ with an AC magnetic field of amplitude 88 mT and a frequency of 108 kHz. Specific absorption rate (SAR) increases with the increased ratio of Al-substituted maghemite. The T_max value for the gels prepared by the mixture of LSMO and Al-substituted maghemite can be adjusted to suit therapeutic temperature. The time required to reach optimum temperature decreased with the increased ratio of later. Such biphasic gel could be very useful for magnetic hyperthermia with in vivo control of temperature.     

A non-iterative partial discharge source location method for transformers employing acoustic emission techniques

Partial discharge (PD) causes premature insulation failure of transformers. It is essential to detect PD to avoid unwanted failure of transformers. Only detection of PD is not sufficient for a transformer of huge size, unless it is possible to locate. Acoustic partial discharge measurement is advantageous for PD source location. There are different algorithms for PD source location. These are iterative and require large number of acoustic emission (AE) sensors. This paper presents a non-iterative source location algorithm employing four AE sensors. This algorithm is applied to experimental data. Proposed algorithm is also applied to published data and compared with existing iterative methods. Main error for source location is due to arrival time calculation. In order to reduce the error in AE signal arrival time calculation, different arrival time calculation methods are discussed and a comprehensive method is proposed. By applying these methods, arrival time is calculated from measured signal.