Determination of gallium originated from a gallium-based anticancer drug in human urine using ICP-MS

Abstract

Urine analysis gives an insight into the excretion of the administered drug which is related to its reactivity and toxicity. In this work, the capability of inductively coupled plasma mass spectrometry (ICP-MS) to measure ultratrace metal levels was utilized for rapid assaying of gallium originating from the novel gallium anticancer drug, tris(8-quinolinolato)gallium(III) (GaQ(3)), in human urine. Sample dilution with 1% (v/v) HNO(3) as the only required pre-treatment was shown to prevent contamination of the sample introduction system and to reduce polyatomic interferences from sample components. The origin of the blank signal at masses of gallium isotopes, 71 and 69, was investigated using high-resolution ICP-MS and attributed, respectively, to the formation of (36)Ar(35)Cl(+) and (40)Ar(31)P(+) ions and, tentatively, to a triplet of doubly charged ions of Ba, La, and Ce. The accuracy and precision performance was tested by evaluating a set of parameters for analytical method validation. The developed assay has been applied for the determination of gallium in urine samples spiked with GaQ(3). The achieved recoveries (95-102%) and quantification limit of 0.2 μg L(-1) emphasize the practical applicability of the presented analytical approach to monitor renal elimination of GaQ(3) at all dose levels in clinical trials that are currently in progress.

Inductively Coupled Plasma Mass Spectrometry

“…The urinary excretion of gallium following anticancer treatment by tris(8-quinolinolato)gallium(III) was studied by Filatova et al 302 In their investigation they have identified a couple of polyatomic or doubly charged ions interfering with both isotopes of Ga ( 69 Ga 1 and 71 Ga 1 ) such as 36 Ar 35 Cl 1 , 40 Ar 31 P 1 and 138 Ba 21 , but they could be separated by ICP-SFMS.…”

Evaluation of Gallium as a Tracer of Exogenous Hemoglobin–Haptoglobin Complexes for Targeted Drug Delivery Applications

“…Knowing the Ga/Hp labeling ratio provides an opportunity to determine the concentration of this protein (or protein/drug conjugates) in complex biological matrices by measuring the levels of Ga. Ga can be readily detected in a variety of [52,53]. Figure 5 shows a relevant region of the ICP mass spectrum of a blank (human serum that had not been doped with Ga in any form), where low-abundance ionic signal is observed at both m/z 69 and 71, even though the measurements were carried out in the kinetic energy discrimination (KED) mode to reduce polyatomic interferences.…”

Recent progress of ICP-MS in the development of metal-based drugs and diagnostic agents

“…In testing the solubility of GaQ 3 in simulated intestine juice, the blank signal at the mass of gallium-71 isotope was observed using high-resolution ICP-MS and attributed to the formation of 36 Ar 35 Cl + and 40 Ar 31 P + ions. 18…”