TY - JOUR
T1 - Validated RP-HPLC method for the simultaneous analysis of gemcitabine and LY-364947 in liposomal formulations
AU - Bansal, Shyam S.
AU - Celia, Christian
AU - Ferrati, Silvia
AU - Zabre, Erika
AU - Ferrari, Mauro
AU - Palapattu, Ganesh
AU - Grattoni, Alessandro
PY - 2013/8/15
Y1 - 2013/8/15
N2 - Combined use of gemcitabine (Gem) and LY-364947 (LY), a TGF-β1 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 C18 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.
AB - Combined use of gemcitabine (Gem) and LY-364947 (LY), a TGF-β1 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 C18 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.
KW - Chemotherapeutics
KW - Gemcitabine
KW - Liposomes
KW - LY-364947
KW - RP-HPLC
KW - Simultaneous analysis
UR - http://www.scopus.com/inward/record.url?scp=84881328726&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881328726&partnerID=8YFLogxK
U2 - 10.2174/13894501113149990165
DO - 10.2174/13894501113149990165
M3 - Article
C2 - 23721184
AN - SCOPUS:84881328726
VL - 14
SP - 1061
EP - 1069
JO - Current Drug Targets
JF - Current Drug Targets
SN - 1389-4501
IS - 9
ER -