GLP validation of neratinib from pl

GLP validation of neratinib from plasma (K2EDTA) with a structural analog internal standard (WAY-178357) and separation by protein precipitation and HPLC-MS/MS analysis. Stock solutions in acetonitrile: water (1:1 v/v) were stable for 9 hours at RT and up to 70 days at 2 to 8°C. Standard curves were linear from the LLOQ of 3.00 ng/mL to 250 ng/mL (mean r2 = 0.9917). Selectivity was acceptable and there was no significant carryover. The matrix effect was 14.0%. Mean precision (%RSD) and accuracy (%) for n=6 of the LLOQ were 8.8% and 104.0%, respectively. Mean inter-day and intra-day precision and accuracy for low, mid, and high QCs were acceptable. Neratinib was stable in whole blood stored for up to 2 hours at RT or in an ice bath. Plasma samples could be diluted 1:10 with acceptable accuracy and precision. Processed samples were stable after storage for up to 82 h at 2 to 8°C. The maximum batch size was 96 injections. Long term storage was extended to 2 years at -70°C and 13 months at -20°C for the low and high