Determination of penehyclidine hydrochloride in beagle dog plasma by liquid chromatography-electrospray ionization mass spectrometry and the pharmacokinetic study

To develop a fast and sensitive liquid chromatography-mass spectrometry method for the determination of penehyclidine hydrochloride （PH） in beagle dog plasma. PH and diphenhydramine hydrochloride （internal standard, IS） were extracted with a solvent mixture of petroleum ether-ethyl ether （7：3）. Chromatographic separation was achieved on a reversed-phase Eclipse XDB-C18 column （4.6 mm × 150 mm, 5 um） using the eluent of methanol-water （5 mmol/L ammonium acetate） （90：10, v/v, pH 5.8） as mobile phase. The electrospray ionization source was set at the positive multiple reaction monitoring （MRM） mode. This method involved the use of the [M＋H]^＋ ions of PH and diphenhydramine hydrochloride at m/z 316.4- 128.2 and m/z 256.4-167.2. The calibration curve was linear in the range of 1-1000 ng/mL with a correlation coefficient of 0.9988. The lower limit of quantification was 0.05 ng/mL. The precision, accuracy and recovery of the method were acceptable. Following intravenous injection admires＇ tration at doses of 0.5, 1 and 5 mg/kg PH, the main pharmacokinetic parameters were as the followings, t1/2a 0.33 h, t1/2β 2.44 1% tmax 0.058 1% AUC and Cmax exhibited a linear increase along with the increase of dose. The two-compartment model fit the three dose groups. This method was sensitive, accurate and fast for the determination of concentration of PH in beagle dog plasma. It could be used in pharmacokinetic studies of PH.

Bioavailable curcumin formulations:A review of pharmacokinetic studies in healthy volunteers

Curcumin is a widely studied natural compound which has shown tremendous in vitro therapeutic poten- tial. Despite that, the clinical efficacy of the native curcumin is weak due to its low bioavailability and high metabolism in the gastrointestinal tract. During the last decade, researchers have come up with dif- ferent formulations with a focus on improving the bioavailability of curcumin. As a result, a significant number of bioavailable curcumin-based formulations were introduced with the varying range of enhanced bioavailability. The purpose of this review is to collate the published clinical studies of cur- cumin products with.improved bioavailability over conventional （unformulated） curcumin. Based on the literature search, 11 curcumin formulations with available human bioavailability and pharmacokinet- ics data were included in this review. Further, the data on clinical study design, analytical method, phar- macokinetic parameters and other relevant details of each formulation were extracted. Based on a review of these studies, it is evident that better bioavailability of formulated curcumin products is mostly attrib- uted to improved solubility, stability, and possibly low first-pass metabolism. The review hopes to provide a quick reference guide for anyone looking information on these bioavailable curcumin formulations. Based on the published reports, NovaSol （185）, CurcuWin （136） and LongVida （100） exhibited over 100-fold higher bioavailability relative to reference unformulated curcumin. Suggested mechanisms accounting for improved bioavailability of the formulations and details on the bioanalysis methods are also discussed.