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ABSTRACT Vinblastine and vincristine, both of which are bisindole alkaloids derived from vindoline and catharanthine, have been used for cancer chemotherapy; their monomeric precursor molecules are vindoline and catharanthine. A simple and selective liquid chromatography mass spectrometry method for simultaneous determination of vindoline and catharanthine in rat plasma was developed. Chromatographic separation was achieved on a C18 (2.1 × 50 mm, 3.5 µm) column with acetonitrile-0.1% formic acid in water as mobile phase with gradient elution. The flow rate was set at 0.4 mL/min. An electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring mode was used for quantification. Mean recoveries were in the range of 87.3-92.6% for vindoline in rat plasma and 88.5-96.5% for catharanthine. Matrix effects for vindoline and catharanthine were measured to be between 95.3 and 104.7%. Coefficients of variation of intra-day and inter-day precision were both <15%. The accuracy of the method ranged from 93.8 to 108.1%. The method was successfully applied in a pharmacokinetic study of vindoline and catharanthine in rats. The bioavailability of vindoline and catharanthine were 5.4 and 4.7%, respectively. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

1. Entinostat, also known as SNDX-275 or MS-275, is a novel, potent, orally bioavailable, class I selective histone deacetylase inhibitor. Pre-clinical data has show that MS-275 can enhance the activity of lapatinib in HER2+ metastatic inflammatory and non-inflammatory breast cancer. This study examined whether oral administration of MS-275 to the rats with lapatinib led to any pharmacokinetic interactions. 2. To evaluate pharmacokinetic interaction of MS-275 and lapatinib in rat, a sensitive and simple LC-MS method was developed to simultaneously determine MS-275 and lapatinib in rat plasma with carbamazepine as internal standard (IS). Eighteen rats were divided randomly into three groups, lapatinib group (lapatinib 15 mg/kg, n = 8), MS-275 group (MS-275 15 mg/kg, n = 8) and co-administration group (MS-275 15 mg/kg and lapatinib 15 mg/kg, n = 8). 3. There was no statistical pharmacokinetics difference for MS-275 in MS-275 group and co-administration group; the lapatinib could not influence the pharmacokinetic profile of MS-275 in rats. However, there is a statistical pharmacokinetics difference between lapatinib in the lapatinib group and co-administration group, when co-oral administration MS-275 with lapatinib, AUC increased from 2375.5 to 9900.3 ng/mL h ( p < 0.05), Cmax increased from 538.0 to 2578.2 ng/mL ( p < 0.01), CL decreased from 6.2 to 1.7 L/h/kg ( p < 0.01). 4. These data indicate MS-275 could obviously influence the pharmacokinetic profile of lapatinib in rats, which might cause drug-drug interactions in humans when using lapatinib with MS-275. Further investigations should be carried out to elucidate the synergistic mechanisms between the two drugs. [ABSTRACT FROM AUTHOR]

Andrographolide has a low aqueous solubility and oral bioavailability, which limits its clinical application. Reform the dosage forms of andrographolide to improve its aqueous solubility and oral bioavailability. The formulation, characterisation, stability, anti-inflammatory effect, pharmacokinetics and oral toxicity of andrographolide-loaded microemulsion, were studied. An formulation of O/W microemulsion consisting of an oil phase of isopropyl myristate, a surfactant phase of Tween 80, a co-surfactant of alcohol, and water was found to be ideal, with mean droplet size of 15.9 nm, a high capacity of solubilisation for andrographolide (8.02 mg mL−1). Such an andrographolide-loaded microemulsion is stable by monitoring the time, temperature and gravity-dependent change, and has a much better anti-inflammatory effect and a higher biological availability than andrographolide tablets. Besides, it also shows a very low acute oral toxicity. The andrographolide-loaded microemulsion is a promising dosage form of andrographolide. [ABSTRACT FROM AUTHOR]

Highlights: [•] First report of development an LC–MS method for the determination of solasodine in rat plasma. [•] First report of pharmacokinetic study of solasodine after oral administration. [•] A simple one-step liquid–liquid extraction by ethyl acetate was used for sample treatment. [ABSTRACT FROM AUTHOR]

Highlights: [•] Development and validation of an LC–MS method for the determination of bicuculline in rat plasma. [•] The method successfully applied to pharmacokinetic study of bicuculline after gavage administration. [•] A simple one-step protein precipitation procedure without further cleanup was developed. [ABSTRACT FROM AUTHOR]