Development and validation of a combined liquid chromatography tandem-mass spectrometry assay for the quantification of aprepitant and dexamethasone in human plasma to support pharmacokinetic studies in pediatric patients

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 1171; p. 122639
• Main Authors: Nijstad, A. Laura, Tibben, Matthijs M., Gebretensae, Abadi, Rosing, Hilde, de Vos-Kerkhof, Evelien, Zwaan, C. Michel, Huitema, Alwin D.R., Beijnen, Jos H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2021
• Subjects: Aprepitant; Dexamethasone; Drug-drug interaction; LC-MS/MS; Pediatric oncology; Aprepitant; LLOQ; Dexamethasone; Pediatric oncology; MRM; IS; AUC; P; LC-MS/MS; CINV; QC; CV; LC-MS/M; MF; Drug-drug interaction; ULOQ
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2021.122639

•A sensitive assay for the simultaneous quantification of aprepitant and dexamethasone was developed and validated.•This assay only requires small sample volumes.•The LC-MS/MS method is selective, linear, accurate and precise.•The assay is suitable for pharmacokinetic studies in pediatric patients. A pharmacokinetic study was set up to investigate the pharmacokinetics of the anti-emetic agents aprepitant and dexamethasone and the drug-drug interaction between these drugs in children. In order to quantify aprepitant and dexamethasone, a liquid chromatography-tandem mass spectrometry assay was developed and validated for the simultaneous analysis of aprepitant and dexamethasone. Protein precipitation with acetonitrile-methanol (1:1, v/v) was used to extract the analytes from plasma. The assay was based on reversed-phase chromatography coupled with tandem mass spectrometry detection operating in the positive ion mode. The assay was validated based on the guidelines on bioanalytical methods by the US Food and Drug Administration and European Medicines Agency. The calibration model was linear and a weighting factor of 1/concentration2 was used over the range of 0.1–50 ng/mL for aprepitant and 1–500 ng/mL for dexamethasone. Intra-assay and inter-assay bias were within ±20% for all analytes at the lower limit of quantification and within ±15% at remaining concentrations. Dilution integrity tests showed that samples exceeding the upper limit of quantification can be diluted 100 times in control matrix. Stability experiments showed that the compounds are stable in the biomatrix for 25 h at room temperatures and 89 days at −20 °C. This assay is considered suitable for pharmacokinetic studies and will be used to study the drug-drug interaction between aprepitant and dexamethasone in pediatric patients.