Validated RP-HPLC Method for the Simultaneous Analysis of Gemcitabine and LY-364947 in Liposomal Formulations

被引：6

作者：

Bansal, Shyam S. ^{[1
]}

Celia, Christian ^{[1
,2
]}

Ferrati, Silvia ^{[1
]}

Zabre, Erika ^{[1
]}

Ferrari, Mauro ^{[1
]}

Palapattu, Ganesh ^{[1
,3
]}

Grattoni, Alessandro ^{[1
]}

机构：

[1] Methodist Hosp, Res Inst, Dept Nanomed, Houston, TX 77030 USA

[2] Univ G dAnnunzio, Dept Pharm, I-66013 Chieti, CH, Italy

[3] Methodist Hosp, Dept Urol, Houston, TX 77030 USA

来源：

CURRENT DRUG TARGETS | 2013年 / 14卷 / 09期

关键词：

Chemotherapeutics; gemcitabine; liposomes; LY-364947; RP-HPLC; simultaneous analysis; PERFORMANCE LIQUID-CHROMATOGRAPHY; TGF-BETA; SOLID TUMORS; PHASE-I; CANCER; PLASMA; CHEMORADIATION; METABOLITE; INHIBITORS;

D O I：

10.2174/13894501113149990165

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Combined use of gemcitabine (Gem) and LY-364947 (LY), a TGF-beta 1 receptor inhibitor, has shown promise for the treatment of fibrotic pancreatic cancer, by reducing collagen production and improving tumor drug penetration. The preparation and optimization of novel Gem and LY formulations, including co-encapsulation in liposomes, require a validated method for the simultaneous quantification of both drugs, a method that had yet to be developed. Here we demonstrate an RP-HPLC protocol for the simultaneous detection of Gem and LY at 266 and 228 nm with retention times of 3.37 and 11.34 mins, respectively. The method, which uses a C-18 column and a KH2PO4 (10 mM)-methanol mobile phase, was validated for linearity, precision, accuracy, limits of detection, and robustness. Co-loaded liposomes with both Gem and LY (Gem/LY liposomes) were developed to investigate the protocol applicability to pharmacokinetic analysis and formulation characterization. The method specificity was evaluated in presence of liposomal components in fetal bovine serum (FBS). Finally, the method was demonstrated by quantifying Gem/LY liposomal encapsulation efficiency and concentration liposomes-spiked FBS.

引用

页码：1061 / 1069

页数：9