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.

     

Synthesis and characterization of microcrystalline cellulose powder from corn husk fibres using bio-chemical route

In the present study low cost microcrystalline cellulose (MCC) powder was prepared from cornhusk fibres, extracted chemically followed by anaerobic consortium treatment. Cornhusk fibres were treated with 10% alkali at 120 °C for 60 min followed by anaerobic consortium treatment for 3 days. It was then bleached with hydrogen peroxide and finally washed. Bleached pulp was hydrolysed using 4 N HCl to get the MCC. In the present investigation, we have characterized the MCC prepared from cornhusk fibres thoroughly for its physico-chemical properties and compared with Avicel^®-PH 101, a commercial grade MCC. Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Powder Diffraction (XRD) and Differential Scanning Calorimetry (DSC) were used for characterization of samples. Similarly the powder and flow properties of the MCC prepared from cornhusk fibres were also investigated and the results were compared with Avicel^®-PH 101. Our results showed that various properties and the purity of MCC prepared from cornhusk fibres are comparable to the commercial grade MCC. Since, cornhusk is an agricultural waste product, MCC obtained from cornhusk fibres will be from cheaper raw materials than current market MCC.     

A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the estimation of amlodipine in human plasma

A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the estimation of amlodipine in human plasma. Amlodipine was extracted from human plasma by using a solid-phase extraction technique. Imipramine was used as the internal standard. A Hypersil BDS C18 column provided chromatographic separation of analytes followed by detection with mass spectrometry. The method involves a rapid solid-phase extraction from plasma, simple isocratic chromatography conditions and mass spectrometric detection that enables detection at sub-nanogram levels. The proposed method has been validated for a linear range of 0.1-10.0 ng/mL with correlation coefficient >or=0.9990. The intrarun and interrun precision and accuracy were within 10.0%. The overall recovery for amlodipine was 63.67%. Total run time was 3.2 min only.     

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.     

A comparison of glass forming ability in Ag-Si and Au-Si alloys

Ag-Si alloys of various compositions were produced by laser-induced melting and quenching of vapour-deposited thin films. Despite cooling rates approaching 10¹⁰K/s the procedure fails to yield glassy phases for all compositions except those around 80 at.-% Si. This behaviour contrasts with that of the Au-Si system which under similar experimental conditions yields glasses at almost arbitrary concentrations. The difference in glass forming ability of these two systems, which have similar phase diagrams, is explained in terms of the difference in the heat of mixing of the liquid, and its consequent effect on both the thermodynamics and kinetics of these alloys.     

Rapid and sensitive liquid chromatography-tandem mass spectrometry method for the estimation of nicorandil in human plasma

A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the estimation of nicorandil in human plasma. Nicorandil was extracted from human plasma using solid-phase extraction technique. Imipramine was used as the internal standard. A Betasil C18 column provided chromatographic separation of analytes followed by detection with mass spectrometry. The method involves a rapid solid-phase extraction from plasma, simple isocratic chromatography conditions and mass spectrometric detection that enables detection at nanogram levels. The proposed method has been validated for a linear range of 1.0-500.0 ng/mL with a correlation coefficient of > or =0.9993. The intra-run and inter-run precision and accuracy was within 10.0%. The overall recovery for nicorandil was 63.81%. The total run time was just 3.0 min.     

Quantification of zolpidem in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry

A simple and robust method for quantification of zolpidem in human plasma has been established using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS). Es-citalopram was used as an internal standard. Zolpidem and internal standard in plasma sample were extracted using solid-phase extraction cartridges (Oasis HLB, 1 cm3/30 mg). The samples were injected into a C8 reversed-phase column and the mobile phase used was acetonitrile-ammonium acetate (pH 4.6; 10 mm) (80:20, v/v) at a flow rate of 0.7 mL/min. Using MS/MS in the selected reaction-monitoring (SRM) mode, zolpidem and Es-citalopram were detected without any interference from human plasma matrix. Zolpidem produced a protonated precursor ion ([M+H]+) at m/z 308.1 and a corresponding product ion at m/z 235.1. The internal standard produced a protonated precursor ion ([M+H]+) at m/z 325.1 and a corresponding product ion at m/z 262.1. Detection of zolpidem in human plasma by the LC-ESI MS/MS method was accurate and precise with a quantification limit of 2.5 ng/mL. The proposed method was validated in the linear range 2.5-300 ng/mL. Reproducibility, recovery and stability of the method were evaluated. The method has been successfully applied to bioequivalence studies of zolpidem.     

Rapid and sensitive method for the determination of sibutramine active metabolites in human plasma by reversed-phase liquid chromatography-tandem mass spectroscopy

A new, rapid, and sensitive liquid chromatography-tandem mass spectrometry method is developed and validated to quantitate the sibutramine active metabolites mono desmethyl sibutramine (M1) and di-desmethyl sibutramine (M2) using imipramine as the internal standard in human plasma samples for routine bioequivalence studies. The method involves rapid solid-phase extraction from plasma, eliminating the drying and reconstitution steps. The analytes are chromatographed on a C8 reversed-phase chromatographic column and analyzed by mass spectrometry in the multiple reaction monitoring mode, which enables a quantitation limit at the sub-nanogram level. The method has a chromatographic run time of 2.8 min. The proposed method is validated with a linear range of 0.1-8.0 and 0.2-16.0 ng/mL for M1 and M2, respectively, with a correlation coefficient of regression > or = 0.9990. The method is sensitive and reproducible, having intra- and inter-assay precision at the lower limit of quantitation (0.1 ng/mL for M1 and 0.2 ng/mL for M2) < 10.0%. The overall recovery for M1 and M2 is 93.5% and 77.9%, respectively. The method has been applied to a bioequivalence clinical study with great success.