Determination of Landiolol Concentration in Human Blood by LC-MS/MS / 医药导报

Objective To establish an LC-MS/MS method for the detection of landiolol concentration in human blood.Methods After pretreatment with neostigmine and a deproteinization procedure, landiolol and the internal standard venlafaxine were eluted isocratically using a mobile phase consisting of acetonitrile and 10 mmoL·L-1 ammonium acetate with 0. 1% formic acid in a ratio of 3664 ( V/V ) . Separation of the respective compounds was achieved on a Waters XTerra? RP18 column (150 mmí4. 6 mm,5 μm). Quantitative analysis of landiolol was conducted by a triple-quadrupole mass spectrometer with positive-electrospray ionization source,monitored under a multiple reaction monitoring ( MRM) mode. The extracted ions monitored following MRM transitions were m/z 510. 5→423. 1 for landiolol and m/z 278. 2→215. 1 for the internal standard venlafaxine. ResultsThe calibration curve of landiolol in human blood showed good linear relationship in the range of 1. 010-2 020 μg·L-1 . The lower limit of quantitation was 1. 010 μg · L-1 . The RSD of within-day and between-day precision was less than 6. 5% and 4. 8%, respectively. The recovery rate was 92. 6%-100. 9%. Conclusion The method is proven to be simple,rapid and reliable,and can be applied to study the pharmacokinetics of landiolol hydrochloride in healthy Chinese volunteers.

The pharmacokinetics and sustained release characteristics evaluation of galanthamine hydrohromide sustained release tablet in healthy volunteers / 中国药理学通报

Aim To study the pharmacokinetics characteristics of galanthamine hydrohromide sustained release tablets and conventional tablets in healthy volunteers after a single and multiple oral doses. MethodsA single and multiple oral doses of galanthamine hydrohromide sustained release tablets and conventional tablets were given to 20 healthy male volunteers in a randomized cross-over study. We developed an LC-MS assay using naloxone as the internal standard to determine the plasma concentrations of galanthamine, calculate the pharmacokinetic parameters and evaluate the relative bioavailability and sustained release characteristics of galanthamine hydrohromide sustained release tablet. Results The pharmacokinetic parameters of the sustained release tablet and conventional tablet obtained from the single-dose study were as follows: the HVD_12 C_max(time span during which the plasma concentration is at least half of the C_max value)were (15.4?1.7) h and (5.4?2.5) h, the retard quotients (R△,the HVD_12 C_max ratio of sustained release tablets to conventional tablets) of sustained release tablet was 3.4?1.4, the T_max were (4.4?1.5) h and (1.3?1.2) h, the C_max were (27.5?2.9) ?g?L-1 and (53.7?12.7) ?g?L-1.Results showed significant sustained release characteristics of the sustained release tablet. The relative bioavailability of the sustained release tablet was (95.9?14.2) %。The pharmacokinetic parameters of the sustained release tablet and conventional tablet obtained from the multi-dose study were as follows: the T_max were (3.0?1.6) h and (0.9?0.3) h,the CSS_max were (58.8?9.4) ?g?L-1 and (52.0?6.9) ?g?L-1,the CSS_min were (16.2?4.0) ?g?L-1 and (22.5?5.0) ?g?L-1,the C_av were (39.0?3.9) ?g?L-1 and (37.1?5.0) ?g?L-1,the DF were 1.1 ?0.3 and 0.8?0.1, respectively. Results of two one-side t test showed that AUC_SS、CSS_max、C_av of two tablets were bioeqivalent. Conclusion Results showed that the sustained release tablet and the regular tablet were bioequivalent in absorbed extent, and the sustained release tablet exhibited a good retarding effect in release.