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

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2022-01, Vol.1188, p.123078-123078, Article 123078
• Main Authors: Kim, Taeheon, Choi, Seungmok, Lim, Duck-soo, Yun, Hwi-yeol
• Format: Article
• Language: English
• Subjects: Animals; Beagle dog; Bioanalysis; Chromatography, Liquid - methods; Dogs; Injections, Subcutaneous; Lanreotide; Limit of Detection; Linear Models; Male; Peptides, Cyclic - administration & dosage; Peptides, Cyclic - blood; Peptides, Cyclic - pharmacokinetics; Pharmacokinetics; Reproducibility of Results; Somatostatin - administration & dosage; Somatostatin - analogs & derivatives; Somatostatin - blood; Somatostatin - pharmacokinetics; Somatuline Depot; Tandem Mass Spectrometry - methods; UPLC-MS/MS
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2021.123078

•A simple, sensitive and validated quantification method of lanreotide in beagle plasma is developed using UPLC-MS/MS systems.•It is the fitst LC-MS/MS method of lanreotide in plasma.•The calibration curve range of lanreotide is from 0.3 (LLOQ) to 1000 ng/mL in beagle plasma.•The pharmacokinetic profile and parameters of lanreotide in beagle dogs after single subcutaneous injection were reported. 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 → 170.0 for lanreotide [M + 2H]2+ and 472.2 → 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