Fu, Yunlin, Li, Wenkui, Flarakos, Jimmy and Tse, Francis (2016) LC-MS/MS determination of Pasireotide (SOM230), a cyclic peptide, in monkey plasma. Journal of Chromatography B.

Abstract

A novel liquid chromatographic method with tandem mass spectrometric detection (LC-MS/MS) for the determination of Pasireotide (SOM230) was developed and validated with dynamic ranges of 0.500 to 250 ng/mL using 0.0500 mL of monkey plasma. SOM230 and the internal standard, [M+6]SOM230, were extracted from monkey plasma via µElution SPE. The acidified sample matrix was loaded onto the preconditioned Waters WCX plate for further processing. The analyte was eluted from the SPE plate using freshly prepared elution solvent, followed by dilution and LC-MS/MS analysis. The optimal chromatographic separation was achieved on an Atlantis dC18 (50 x 2.1 mm, 5 µm particle size) column using gradient elution. The total analysis cycle time is approximately 3.5 min per injection. Trifluoroacetic acid (TFA) (0.05%, v/v) and acetic acid (0.5%, v/v) were incorporated into the mobile phases to improve the chromatographic performance and to minimize the carryover due to nonspecific binding of the analyte to the walls of 96-well plate. The current method was validated for sensitivity, selectivity, linearity, reproducibility, stability and recovery. The accuracy and precision for the LLOQs (0.500 ng/mL) were within ±5.6% bias and ≤7.8 % CV, respectively. During the intra-day and inter-day evaluations the QC sample (1.50, 7.50, 75.0 and 190 ng/mL) precision ranged from 2.7 to 4.9% CV and the accuracy (% bias) from -1.3 to 7.3%, respectively. Additional assessments of incurred sample reanalysis (ISR) were conducted to demonstrate the ruggedness and robustness of the assay method. The validated method was successfully used to support a toxicity study in monkeys administered with 5 and 30 mg of SOM230 in a single intramuscular injection of a long acting release (LAR) formulation.

Item Type:	Article
Keywords:	Pasireotide, SOM230, LC-MS/MS, quantification, monkey plasma, SPE, µElution
Date Deposited:	27 Apr 2016 23:45
Last Modified:	27 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/25230