Development and validation of an LC-MS/MS method for quantitative determination of GS87, a novel antineoplastic agent, in mouse plasma

Journal of Pharmaceutical and Biomedical Analysis
Sandeep R KunatiYan Xu

Abstract

GS87 is a novel, highly specific GSK3 inhibitor, which has shown to induce extensive differentiation of acute myeloid leukemia (AML) cells in early mouse studies and has great potential for therapeutic advancement. This work described the development and validation of an LC-MS/MS method for quantitative determination of GS87 in mouse plasma. In this method, GS87 and T6447952 (a structural analog used as internal standard) were extracted from plasma using hexane as extraction solvent, and separated isocratically on a Waters XTerra® MS C8 column (2.1 × 50 mm, 3.5 μm) using a mobile phase consisting of acetonitrile and 5.00 mM ammonium formate (35:65, v/v) pumped at a flow rate of 0.200 mL min-1. Quantitation of GS87 was done by positive electrospray ionization tandem mass spectrometry operated in multiple-reaction-monitoring (MRM) mode. The method has been validated in accordance with the US Food and drug administration guidelines for bioanalytical method validation. It has linear calibration range of 2.50-250 ng mL-1 with correlation coefficient of >0.999. The intra- and inter- assay accuracy and precision were ≤ ±5 and ≤6%, respectively. The IS normalized recovery of GS87 was 103-106%. The stability studies showed that GS87 was...Continue Reading

Related Concepts

Related Feeds

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.