Hybrid solid-phase extraction to overcome interference due to phospholipids for determination of neratinib in human plasma using UPLC–MS/MS
Funding information: This review work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Funding information: Human Resource Development Group-Council of Scientific & Industrial Research, Grant/Award Number: 09/0702020EMR-I
A reliable and robust bioanalytical method was developed to quantify neratinib, a tyrosine kinase inhibitor in human plasma, using UPLC–MS/MS. The extraction of neratinib and its deuterated internal standard, neratinib-d6, was successfully performed on hybrid solid-phase extraction ultra-cartridges to remove the interference of phospholipids and proteins. Chromatographic analysis was performed on a UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column using 0.1% formic acid and acetonitrile under gradient conditions. The total analysis time was 1.5 min. Neratinib was quantified using electrospray ionization source operated in the positive-ion multiple reaction monitoring mode. The mass transitions of neratinib and neratinib-d6 were m/z 557.3/112.1 and m/z 563.1/118.2, respectively. The linear concentration range for neratinib was 0.5–500 ng/mL, which adequately covers concentration levels expected in real subject samples. The assay was extensively validated for various validation parameters following standard guidelines for a bioanalytical assay. The intra- and inter-batch precision was ≤4.6%, and neratinib was found to be stable under various stability conditions. The mean internal standard–normalized matrix factor and recovery were 0.997 and 95.4%, respectively. The validated method was successfully applied to a pharmacokinetic study in healthy subjects with different doses.
CONFLICT OF INTEREST
The authors declare that there are no conflicts of interest.
DATA AVAILABILITY STATEMENT
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|bmc5416-sup-0001-Supplementary Material.docWord document, 4.6 MB||
TABLE S1 Optimized mass spectrometer working parameters
TABLE S2 Mean pharmacokinetic parameters (±SD) after oral administration of 120 and 240 mg neratinib to 12 healthy Indian subjects under fasting
FIGURE S1 Injection of extracted blank human plasma during post-column infusion of (a) neratinib (200.0 ng/mL) and (b) neratinib-d6
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