Pharmacokinetics of epirubicin hydrochloride long-circulating thermosensitive liposomes in rat plasma / 药学学报
Acta Pharmaceutica Sinica
;
(12): 365-370, 2010.
Article
Dans Chinois
| WPRIM
| ID: wpr-250578
ABSTRACT
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 (8020). 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.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Sang
/
Vecteurs de médicaments
/
Pharmacocinétique
/
Épirubicine
/
Reproductibilité des résultats
/
Chromatographie en phase liquide
/
Sensibilité et spécificité
/
Rat Sprague-Dawley
/
Aire sous la courbe
/
Spectrométrie de masse en tandem
Type d'étude:
Etude diagnostique
/
Étude pronostique
Limites du sujet:
Animaux
langue:
Chinois
Texte intégral:
Acta Pharmaceutica Sinica
Année:
2010
Type:
Article
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