A novel and fully validated hydrophilic interaction liquid chromatography with tandem mass spectrometry method for the determination of intact carboplatin in human plasma

Abstract

Carboplatin is an anticancer drug widely used to treat a variety of cancers. However, a simple, sensitive and rapid method for the quantitation of intact carboplatin is still absence for therapeutic drug monitoring or clinical trials. In this work, a rapid, universal, and reliable hydrophilic interaction liquid chromatography with tandem mass spectrometry method for the determination of intact carboplatin in human plasma was developed and fully validated. Carboplatin was extracted from human plasma by simple protein precipitation with acetonitrile. A good chromatographic separation of carboplatin was achieved on a Waters XBridge HILIC column (2.1 × 150 mm, 3.5 μm), with the analytical time 5.5 min for one sample. The linearity range of the assay was from 10 to 2000 ng/mL. The method was linear (r2 > 0.9989), accurate (<6% bias, 12% bias at LOQ) and precise (intra‐day and inter‐day precision of <3% coefficient of variation). The stability of intact carboplatin in human plasma with three different anticoagulants was assessed in this study. Furthermore, the matrix effect of hemolysis and hyperlipidemic samples was also evaluated for the first time. This work made the routine determination of intact carboplatin feasible and universal in clinical practice.

Systemic Evaluation on the Pharmacokinetics of Platinum-Based Anticancer Drugs From Animal to Cell Level: Based on Total Platinum and Intact Drugs

“…Although distinguished systemic pharmacokinetics of cisplatin, carboplatin, and oxaliplatin has already been investigated extensively and reviewed numerously (O'Dwyer et al, 2000), most of the previous reports are only based on quantification of total platinum with a lack of determination of intact drugs. In addition, several studies on the pharmacokinetics of platinum analogues with quantification of intact drugs have also been reported (Xie et al, 2017;Qin et al, 2018;Ren et al, 2018). However, there is still lack of simultaneous determination of both total Pt and intact drugs to characterize the pharmacokinetics of platinum-based drugs, which can help understand the behaviors of intact platinum-based drug and its biotransformation better.…”

Systematic evaluation of selected supercritical fluid chromatography diol‐ and diethylamine‐based columns for application in hydrophilic interaction liquid chromatography

“…HPLC separations based on the HILIC principle using acetonitrile (ACN) as the main component of the mobile phase can be dated more than 50 years ago [4,5]. In the past decade HILIC has become a first-choice technique for analysis of polar compounds in glycomics [6], proteomics [7] and metabolomics [8] research, and for the analysis of the biologically important compounds such as pharmaceuticals [9,10], amino acids (AAs), peptides and proteins [11][12][13][14]. The HILIC separation system is based on the combination of a hydrophilic stationary phase (SP) and mobile phase composed of less polar organic solvent (usually ACN) and water as a strong eluent.…”

“…HPLC separations based on the HILIC principle using acetonitrile (ACN) as the main component of the mobile phase can be dated more than 50 years ago . In the past decade HILIC has become a first‐choice technique for analysis of polar compounds in glycomics , proteomics and metabolomics research, and for the analysis of the biologically important compounds such as pharmaceuticals , amino acids (AAs), peptides and proteins .…”