PK study of octreotide based on LC-MS/MS combining protein precipitation and impurity extraction technique.
OBJECTIVE
To establish a robust methodology for quantitative analysis of therapeutic peptide in biological samples.


METHODS
Octreotide was chosen as a model therapeutic peptide, and oxidized-octreotide was synthesized as internal standard. Protein precipitation combining liquid-liquid extraction technique was adopted to enhance the recovery and reduce the endogenous interferences effectively. A LC-MS/MS method for the quantification of octreotide in plasma has been optimized and validated according to FDA guidelines.


RESULTS
Linearity, selectivity, accuracy, precision, stability, matrix effect and recovery were within bioanalytical method validation acceptance criteria as FDA guidelines. The methodology was then successfully applied into the studies for octreotide.


CONCLUSIONS
This robust methodology would be useful for the PK studies for octreotide and other therapeutic peptides.
Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
Qian
Q
Wang
Yan
Y
Liang
Tai
T
Rao
Lin
L
Xie
Wei
W
Ye
Hanxu
H
Fu
Lijun
L
Zhou
Rong
R
Xing
Yuhao
Y
Shao
Jingcheng
J
Xiao
Dian
D
Kang
Guangji
G
Wang
D053000:Analytic Sample Preparation Methods; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods* / Q000592:standards; D007275:Injections, Intravenous; D059625:Liquid-Liquid Extraction / Q000379:methods*; D008297:Male; D015282:Octreotide / Q000008:administration & dosage / Q000032:analysis / Q000302:isolation & purification* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards
D015282:Octreotide