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The authors proposed a sensitive, selective and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay procedure for the quantification of lurasidone and its active metabolite, i.e. ID-14283 in human plasma simultaneously using corresponding isotope labeled compounds as internal standards as per regulatory guidelines. After liquid-liquid extraction with tert-butyl methyl ether, the analytes were chromatographed on a C18 column using an optimized mobile phase composed of 5 mm ammonium acetate (pH 5.0) and acetonitrile (15:85, v/v) and delivered at a flow rate of 1.00 mL/min. The assay exhibits excellent linearity in the concentration ranges of 0.25-100 and 0.10-14.1 ng/mL for lurasidone and ID-14283, respectively. The precision and accuracy results over five concentration levels in four different batches were well within the acceptance limits. Lurasidone and ID-14283 were found to be stable in battery of stability studies. The method was rapid with the chromatographic run time 2.5 min, which made it possible to analyze 300 samples in a single day. Additionally, this method was successfully used to estimate the in vivo plasma concentrations of lurasidone and ID-14283 obtained from a pharmacokinetic study in south Indian male subjects and the results were authenticated by conducting incurred samples reanalysis. Copyright © 2015 John Wiley & Sons, Ltd.

Background: A series of novel 2 substituted 4-anilinoquinazolines-pyrrole hybrids were synthesized, and cytotoxic activity were evaluated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Methods: The cell line used for the activity was MCF-7 breast cancer cell line and A459 human lung adenocarcinoma cell line. The newly quinazoline-pyrrole hybrid compounds have been synthesized from the 4chloro-7-(3-chloropropoxy)-6-methoxy-2-phenylquinazoline derivatives. The chemical structure of the synthesized compounds has been confirmed by FTIR, 1 HNMR, 13 C NMR, and mass spectral data. The cytotoxic study was conducted using morphological study and MTT assay against adenocarcinoma and human breast cancer cell lines. Results: The results of cytotoxic evaluation revealed that few compounds show moderate to promising activity when compared with standard doxorubicin (IC 50 value 41.05 μM at 72 h). The synthesized compounds 7d and 7f were found effective in breast cancer cell line with IC 50 values 40.64 μM and 44.98 μM at 72 h, respectively. The synthesized compounds 7d, 7f, 7g, and 7h were found effective in adenocarcinoma cell line with IC 50 values of 41.05 μM, 45.54 μM, 46.93 μM, and 48.62 μM, respectively. Conclusion: Based on the experimental evidences, we proposed structure activity relationship to provide significant information for the design and development of further potent anticancer agents.

This paper describes a simple, rapid and sensitive liquid chromatography/tandem mass spectrometry assay for the determination of aliskiren in human plasma using nevirapine as an internal standard. Analyte and the internal standard were extracted from 100 μL of human plasma via liquid-liquid extraction using tert-butyl methyl ether. The chromatographic separation was achieved on a C18 column using a mixture of acetonitrile and 0.1% formic acid (90:10, v/v) as the mobile phase at a flow rate of 0.9 mL/min. The calibration curve obtained was linear (r(2) ≥ 0.99) over the concentration range of 0.10-1013 ng/mL. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. A run time of 2.2 min for each sample made it possible to analyze a greater number of samples in a short time, thus increasing the productivity. The proposed method was found to be applicable to clinical studies.

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