A Highly Sensitive Nonextraction-Assisted HPLC Method with Fluorescence Detection for Quantification of Duvelisib in Plasma Samples and its Application to Pharmacokinetic Study in Rats

Abstract

Background

Duvelisib (DUV) is a new oral phosphoinositide-3-kinase (PI3K)-δ and PI3K-γ inhibitor. It has been recently granted an accelerated approval for treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). It is also effective in therapy of T-cell lymphoma, solid tumors, and non-Hodgkin’s lymphoma. In literature, there is no method valid for quantitation of DUV in human plasma for its therapeutic monitoring and pharmacokinetic studies.

Purpose

The purpose of this study is the establishment of a highly sensitive HPLC method with fluorescence detection for quantitation of DUV in plasma for its therapeutic monitoring and pharmacokinetic studies of DUV.

Methods

The resolution of DUV and the internal standard (IS) olaparib (OLA) was achieved on Nucleosil CN column, with a mobile phase composed of acetonitrile:water (25:75, v/v) at a flow rate of 1.7 mL min^–1. The fluorescence of both DUV and OLA was detected at 410 nm after excitation at 280 nm. The method was validated according to the guidelines of bioanalytical method validation.

Results

The method was linear in the range of 5–100 ng mL^–1, and its limit of detection (LOD) and limit of quantitation (LOQ) were 2.12 ng mL^–1 and 7 ng mL^–1, respectively. The precisions of the method were ≤ 8.26%, and its accuracies were ≥ 95.32%. All the other validation parameters were satisfactory. The proposed method was successfully employed to the investigation of the pharmacokinetic profile of DUV in rats following a 25 mg/kg single dose of oral administration.

Conclusion

The method is characterized with high sensitivity, accuracy, simple sample pretreatment, rapidity, eco-friendly as it consumes low volumes of organic solvent in the mobile phase and has high analysis throughput as its run time was short (~ 10 min).

Keywords:

• leukemia
• phosphoinositide-3-kinase
• duvelisib; DUV
• human plasma
• therapeutic drug monitoring
• pharmacokinetic study

Acknowledgments

The authors would like to extend their appreciation to the Deanship of Scientific Research at King Saud University for its funding of this research through the research group project No. RGP-225.

Abbreviations

DUV, duvelisib; PI3K, phosphoinositide 3-kinase; CLL, chronic lymphocytic leukemia; FDA, US Food and Drug Administration; HPLC, high performance liquid chromatography; FD, fluorescence detection; UPLC, ultraperformance liquid chromatography; MS/MS, tandem mass spectrometry; OLA, olaparib; IS, internal standard; ICH, The International Conference on Harmonization; LOD, limit of detection; LOQ, limit of quantification; QC, quality control; RSD, relative standard deviation; AUC, area under curve.

Ethics Statement

Human plasma was obtained from the Blood Bank of King Khalid Hospital of King Saud University (Riyadh, Saudi Arabia). Samples were collected from a healthy volunteer after receiving the consent, and the guidelines outlined in the Helsinki were followed. All procedures performed in studies involving experimental animals were in accordance with the ethical standards for conducting studies on Living Creatures at King Saud University (Riyadh, Saudi Arabia). The study, presented in this manuscript, was approved by the Research Ethics Committee (RCE) of King Saud University with Ethics Reference No: KSU‐SE‐20‐51.

Disclosure

The authors report no conflicts of interest for this work.