Determination of tranilast in bio-samples by LC-MS/MS: Application to a pharmacokinetic and brain tissue distribution study in rats.

As a potent drug used to improve the neurodegenerative conditions, there is few information about the brain tissue distribution of tranilast by now. In this study, a novel sensitive LC-MS/MS method has been developed and validated to determine tranilast in rat brain tissue samples. The calibration curve showed good linearity ranged from 2.140 to 428.0ng·mL-1. The method was fully validated and successfully applied in the brain tissue distribution study of tranilast in rats, which had never been reported in detail by now. Furthermore, a rapid LC-MS/MS method with a short run time of 3min was developed and validated for the determination of tranilast in rat plasma and the application to a pharmacokinetic study of tranilast in rats. After oral dosage of 10.5mg·kg-1 tranilast, the maximum plasma concentration (Cmax1) of tranilast was (18.59±5.40) µg·mL-1 at (0.667±0.408) h while the area under the curve (AUC0-24) was (54.87±14.13) µg·h·mL-1 with the elimination half-life of (2.93±0.41) h. The ratio calculated by dividing the concentration of tranilast in brain with the concentration of tranilast in the plasma, was (0.6042%±0.0572%), (0.7484%±0.0883%), (0.5914%±0.0416%) and (0.3830%±0.1632%) at 0.167, 0.5, 2 and 8h, respectively. The results showed that tranilast with fast absorption could penetrate the rat brain blood barrier after oral gavage. The obtained data also showed that tranilast could be quickly distributed and eliminated in brain tissue.

Simultaneous Determination of a Fixed-Dose Combination of Lercanidipine and Valsartan in Human Plasma by LC-MS-MS: Application to a Pharmacokinetic Study.

A simple, sensitive and reproducible liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS-MS) method was developed and validated for the first time for simultaneous quantification of lercanidipine and valsartan in human plasma. The analytes were extracted by simple protein precipitation with acetonitrile and separated on a Hanbon Hedera ODS-2 C18 (150 mm× 2.1 mm, 5 µm) column. The mobile phase was composed of a mixture (53:47, v/v) of acetonitrile and 10 mmol/L ammonium acetate containing 0.5% formic acid. The analytes were ionized by positive electrospray ion and detected in the multi-reaction monitoring mode with m/z 612.1 → 280.2 for lercanidipine, m/z 436.0 → 235.1 for valsartan and m/z 285.1 → 193.1 for diazepam, the internal standard. The calibration curves obtained were linear over the concentration range of 0.01504-10.07 ng/mL for lercanidipine and 5.025-6,030 ng/mL for valsartan. The results of the intra- and inter-day precision studies were within the acceptance range. The recoveries of the analytes were in the range of 98-103%. This method was successfully applied to the pharmacokinetic study of a novel fixed-dose combination of lercanidipine and valsartan formulation after an oral administration to healthy Chinese subjects.