Bioanalysis of lanreotide in dog plasma using liquid chromatography-tandem mass spectrometry and its application in a pharmacokinetic study of beagle dogs after single subcutaneous injection.
J Chromatogr B Analyt Technol Biomed Life Sci
; 1188: 123078, 2022 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-34891048
ABSTRACT
Lanreotide is similar to a naturally occurring hormone, somatostatin; thus, it may be used to treat acromegaly or metastatic gastroenteropancreatic neuroendocrine tumours. Here, a bioanalytical method coupling ultra-performance liquid chromatography with tandem mass spectrometry to quantify lanreotide and an internal standard (IS) was developed and validated in dog plasma. The plasma samples were extracted using typical protein precipitation processes. The analyte and internal standard were separated on Phenomenex Kinetex® C18 with 0.1% formic acid and acetonitrile in the mobile phase at a flow rate of 0.4 mL/min. The fragmentation of precursor ions to product ions was optimized at m/z 548.8 â 170.0 for lanreotide [M + 2H]2+ and 472.2 â 436.2 for IS [M + H]+. The peak retention times of lanreotide and IS were 1.09 min and 1.22 min, respectively. The calibration curve samples in dog plasma ranged from 0.3 to 1000 ng/mL and showed good linearity, with a correlation coefficient of r2=0.9996. The lower limit of quantitation was 0.3 ng/mL. The intra- and inter-day precision (relative standard deviation) values for each quality control level were < 9.7 % and < 9.3 %, respectively; intra- and inter-day accuracy were < 109.3% and < 110.4%, respectively. Lanreotide in dog plasma was stable in various conditions. The maximum plasma concentration of lanreotide in male beagle dogs after subcutaneous injection of Somatuline® (lanreotide) Autogel 120 mg was 88.1 ng/mL. The half-life (T1/2) of lanreotide in beagle dogs was long, approximately 198.6 h; the area under the plasma-concentration curve from 0 to 840 h (day 35) was 6,995 ngâ
h/mL. This novel quantification method using UPLC-MS/MS was successfully applied to the pharmacokinetic analysis of lanreotide in dog plasma. The results will assist future studies of drug formulation and repurposing.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos Cíclicos
/
Somatostatina
/
Cromatografia Líquida
/
Espectrometria de Massas em Tandem
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article