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Rhodium-catalyzed asymmetric hydrogenation of alkyne-tethered cyclohexadienones enables highly regio- and enantioselective reductive cyclization to afford cis-hydrobenzofurans and cis-hydroindoles in high yields. Desymmetrization of 1,3-diyne-tethered cyclohexadienones was also explored, wherein the intramolecular coordination of a Rh complex with the cyclohexadienone ring induces exclusive regioselectivity. Mechanistic studies including hydrogen–deuterium crossover experiments suggested that hydrogen activation is the rate-determining step for tandem reductive cyclization. Moreover, this highly practical and atom-economical transformation has tolerance to many functional groups with a broad range of substrate scope, allowing further transformations to expand the structural complexity of the bicyclic scaffolds.

Three extraction methods were compared for their efficiency to analyze sitagliptin and simvastatin in rat plasma by LC–MS/MS, including (1) liquid–liquid extraction (LLE), (2) solid phase extraction (SPE) and (3) supported liquid extraction (SLE). Comparison of recoveries of analytes with different extraction methods revealed that SLE was the best extraction method. The detection was facilitated with ion trap-mass spectrometer by multiple reactions monitoring (MRM) in a positive ion mode with ESI. The transitions monitored were m/z 441.1→325.2 for simvastatin, 408.2→235.1 for sitagliptin and 278.1→260.1 for the IS. The lower limit of quantification (LLOQ) was 0.2 ng/mL for sitagliptin and 0.1 ng/mL for simvastatin. The effective SLE offers enhanced chromatographic selectivity, thus facilitating the potential utility of the method for routine analysis of biological samples along with pharmacokinetic studies.

The enantioselective desymmetrization via remote C(sp 2 )−H amidation of the prochiral 2,2-disubstituted cyclopentene-1,3-dione with N-methoxybenzamide has been developed. The overall process was catalyzed by a chiral bifunctional thiourea catalyst through a sequential conjugate-additioneliminationtautomerization. This strategy provides rapid access to highly functionalized five-membered carbocycles, bearing an all-carbon quaternary stereogenic center through remote stereocontrol in high yields with moderate to excellent enantioselectivities.

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A novel bioanalytical method was developed and validated for the quantitative determination of darunavir (DRV) in rat plasma by employing hydrophilic interaction chromatography and tandem mass spectrometry (HILIC–MS/MS) with supported liquid extraction (SLE). Irbesartan (IRB) was used as an internal standard (IS). The analyte in rat plasma (200 µL) was isolated through SLE using ethyl acetate as the eluting solvent. The chromatographic separation was achieved on Luna-HILIC (250 mm×4.6 mm, 5 μm) column with a mobile phase of 0.1% of formic acid in water:acetonitrile (5: 95, v/v), at a constant flow rate of 1.0 mL/min. The MS/MS ion transitions for DRV (548.1→392.0) and IS (429.2→207.1) were monitored on an ion trap mass spectrometer, operating in the multiple reaction monitoring (MRM) mode. The lower limit of quantitation (LLOQ) was 0.2 ng/mL and quantitation range was 0.2–5000 ng/mL. The method was validated for its selectivity, sensitivity, carryover, linearity, precision, accuracy, recovery, matrix effect and stability. The method was successfully applied to pharmacokinetic study in rats.

A liquid chromatography–high resolution mass spectrometry (LC–HRMS) method was developed and validated for the determination of piperine (PPR) on dried blood spots (DBS). DBS samples were prepared by spiking the whole blood with analyte to produce 30 µL of blood spots on specimen collection cards. Chromatographic separation was achieved on an Atlantis dC18 column using acetonitrile and water (0.1% formic acid) (85:15, v/v) as mobile phase in an isocratic mode of elution at a flow rate of 0.75 mL/min. MS detection was carried out in electrospray positive ion mode for the target ions and monitored at m/z 286.1465 for PPR and 272.1303 for the internal standard (IS). The developed method exhibited a linear dynamic range over 0.01–2000 ng/mL for PPR on DBS. The overall extraction recovery of PPR from DBS was 92.5%. Influence of hematocrit and spot volume on DBS was also evaluated and found to be well within the acceptable limits. The method was successfully applied to pharmacokinetic studies of PPR in rats.