RESUMEN
Objective:To estimate the pharmacokinetics for two solution types of propofol glycoside in-jections in rats .Methods:A high performance liquid chromatography-high resolution mass spectrometry ( HPLC-MS) was established for measuring propofol in rat plasma .Two kinds of propofol glycoside injec-tions were developed and intravenously administered to rats via tail vein , respectively , and a commercial-ly available propofol emulsion injection was intravenously administered as a control .Propofol plasma concentration-time curves were determined , and the pharmacokinetic parameters were estimated .Re-sults:HPLC-MS measurement was performed by using a quadrupole-orbit trap high-resolution mass spec-trometer on a C18 chromatographic column.The mobile phase consisted of water and methanol (20∶80, V/V) .The ion source was an atmospheric pressure chemical ion source , and the negative ion was used for detection with a scanning mode of selective ion monitoring in which m/z 177.127 4 was used for propofol and m/z 149.096 1 used for thymol as an internal standard .A linear correlation between con-centration and peak area ratio was constructed in the range of 50 μg/L-10.0 mg/L propofol.The limit of quantification was 50μg/L propofol .The average recoveries of propofol from plasma were in the range of 93.6% -101.1%, and intra-day or inter-day relative standard deviation for measurement was <14%.The pharmacokinetic results showed that the two kinds of propofol glycoside injections exhibited the same pharmacokinetic behavior .However, the clearance and area under curve values of propofol for the two propofol glycoside injections were evidently increased as compared with those for propofol emulsion injection, respectively.Furthermore, their apparent distribution volumes were increased as well .Never-theless, the propofol elimination half-life (t1/2) value of the newly developed propofol glycoside injections was the same as that of commercial propofol emulsion injection (approximately 1.5 h).Conclusion:The established HPLC-MS method can be used for measuring propofol concentration accurately in rat plasma . The clearance and distribution volumes of propofol glycoside injection are bigger than those of the propofol emulsion injection .
RESUMEN
To develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of epirubicin hydrochloride (EPI) in rat plasma, daunorubicin hydrochloride was used as internal standard. The plasma samples were deproteinated with methanol, and separation was performed on a reversed-phase CAPCELL PAK C18 column (3.0 mm x 50 mm, 3 microm). The mobile phase contained methanol-0.1% formic acid (80:20). Detection was carried out by multiple reaction monitoring on a HP1200-6410 QQQ LC/MS system. Different preparations of EPI solution, EPI-LIP (EPI-liposome) and EPI-LTSL (EPI-thermosensitive liposome) was administered in rats by i.v with the same dosage (12 mg kg(-1)). The pharmacokinetic model and parameters were fitted and calculated by the DAS ver2.0 software. The calibration curve was linear in the range of 0.01-50 microg mL(-1). The limit of quantification was 0.01 microg mL(-1). RSDs of intra- and interbatch precisions were all less than 11.9%. The average extract recovery was 89.3% and 92.1%, respectively. The pharmacokinetics of EPI in rats with all preparations were fitted to three compartments, which all fast distributed and slowly eliminated. The t1/2 alpha, t1/2 beta, t1/2 gamma, AUC(0-infinity), and MRT(0-infinity) of EPI-LTSL group were 7.5, 1.3, 12.6, 12.9, 3.7 times those of EPI solution group; and 1.6, 1.4, 12.3, 2.9, 2.6 times those of EPI-LIP group. Moreover, the CL of the latter two groups was about 13.4 times of the former EPI-LTSL group. EPI-LTSL can significantly improve AUC and prolong the circulation time of EPI in rat plasma.