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A selective, sensitive, high pressure liquid chromatography-positive electrospray ionization tandem mass spectrometry method was developed and validated for the quantification of aripiprazole in human K(2)EDTA plasma using zolpidem tartrate as an internal standard. The analyte and internal standard were extracted from human plasma by solid-phase extraction using methanol. The eluted samples were chromatographed on a Grace Smart RP 18 4.6 × 100 mm, 3 µ column by using a 95:5 v/v mixture of methanol and ammonium acetate buffer (30 mM, pH 5.0 ± 0.05) as a gradient mobile phase at a flow rate of 0.6 mL/min, and analyzed by mass spectrometry in the multiple reaction monitoring mode using the [M + H](+) ions m/z 448.03 → 285.14 for aripiprazole and m/z 308.13 → 235.25 for the internal standard (zolpidem tartrate), respectively. Calibration plots were linear over the concentration range of 0.20 to 60.01 ng/mL. Intra-day and inter-day precision (percent coefficient of variation) and accuracy (percent nominal) for quality control samples (0.60, 30.60 and 45.59 ng/mL) ranged between 2.28 and 8.93% and between 92.50 and 107.07%, respectively. Extraction recovery of aripiprazole from plasma was in the range 75.56-79.57%; mean recovery was 77.35%. The main pharmacokinetic parameters were T(max) = (4.00 ± 2.336) C(max) = (55.16 ± 13.490) and AUC = (1846.28 ± 484.686).

A selective, high sensitive and high throughput liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) method has been developed and validated for the chromatographic separation and quantitation of duloxetine in human EDTA plasma using fluoxetine (IS) as an internal standard. Analyte and IS were extracted from human plasma by liquid-liquid extraction using MTBE-n Hexane (80:20).The eluted samples were chromatographed on X-terra RP8 (50 mmx4.6 mm, 5 μm particle size) column by using mixture of 30 mM ammonium formate (pH-5.0±0.05) and acetonitrile as an isocratic mobile phase at a flow rate of 0.40 mL/min and analyzed by mass spectrometer in the multiple reaction monitoring (MRM) using the respective m/z 298.08→154.0 for duloxetine and 310.02→148.07 for IS. The linearity of the response/ concentration curve was established in human plasma over the concentration range 0.100-100.017 ng/mL. The lower detection limit (LOD,S/N>3) was 0.04 ng/mL and the lower limit of quantization (LOQ,S/N>10) was 0.100 ng/mL. This LC-MS/MS method was validated with Intra-batch and Inter-batch precision of 5.21-7.02. The Intra-batch and Inter-batch accuracy was 97.14-103.50 respectively. Recovery of duloxetine in human plasma is 80.31% and ISTD recovery is 81.09%. The main pharmacokinetic parameters were Tmax(hr) = (7.25±1.581), Cmax(ng/mL) (44.594±18.599), AUC0→t, = (984.702±526.502) and AUC0→∞, (1027.147±572.790) respectively.

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.

& A highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS=MS) method was developed and validated for the quantification of venlafaxine (VEN) and its active metabolite O-desmethyl venlafaxine (ODV) in human plasma using fluoxetine as an internal standard. The VEN and ODV were extracted by liquid-liquid extraction using MTBE-n Hexane (60:40), and chromatographed on X-terra RP8 (50 mm  4.6 mm, 5-lm particle size) column eluted with a isocratic mobile phase of 10 mM Ammonium acetate (pH 4.50 AE 0.05) and acetonitrile in 10:90 (v=v). The detection was performed by positive ion electrospray ionization in multiple reactions monitoring mode, monitoring the transitions m=z 278.27! 121.08 and 264.33 ! 57.72 for venlafaxine and O-desmethyl venlafaxine, respectively. The assay was linear over the concentration ranges of 0.100-300.010 ng=mL for VEN and 0.200-600.050 ng=mL for ODV with limits of detection and quantification of 0.050 ng=mL for VEN and 0.100 ng=mL for ODV, respectively. This LC-MS=MS method was validated with Intra-batch and Inter-batch precision 1.65-10.80 for VEN and 1.27-7.08 for ODV, respectively. The Intra-batch and Inter-batch %accuracy was 91.77%-104.39 % for VEN and 95.87%-106.28% for ODV, respectively. This method was successfully applied to a pharmacokinetic study of venlafaxine hydrochloride extended release capsules 150 mg steady-state bioequivalence study.