A high performance liquid chromatography ? inductively coupled plasma-mass spectrometry interface employing desolvation for speciation studies of platinum in chemotherapy drugs

Abstract

A novel interface between high performance liquid chromatography (HPLC) and inductively coupled plasma-mass spectrometry (ICP-MS) is described. The eluent from the HPLC is nebulised into a heated cyclone spray-chamber and the solvent removed using a Nafion membrane drier, held at 75 degrees C, and a cryogenic condenser. The condenser consists of 6 Peltier heat pumps connected to liquid cooled aluminium blocks. At a nebuliser gas flow rate of 0.6 l min(-1), the membrane drier removes 58% of the vapour and the Peltier condenser 75% of the remaining vapour, i.e. a total desolvation efficiency of 89%. This enables the use of HPLC solvents which otherwise would destabilise the ICP, e.g. 100% acetonitrile or methanol, and permits the use of solvent gradients with minimal baseline drift. The system has been applied to the determination of platinum species in an organoplatinum drug used for chemotherapy in human plasma ultrafiltrate of patients treated with this new drug (JM-216). The limit of detection for platinum species has been 0.6 ng nl(-1) (i.e. 120 pg of Pt) and several species have been separated with good resolution.

The application of inductively coupled plasma mass spectrometry in clinical pharmacological oncology research

“…As the eluent composition changes, the nature of the plasma changes, which could lead to a variable sensitivity during the gradient TABLE 6. Speciation of metal-based anticancer compounds in environmental samples (NS, not specified) elution and thus calibration problems (Cairns, Ebdon, & Hill, 1996). Furthermore, the presence of high levels of organic solvent or dissolved solids (e.g., salts) can result in constriction of the cone orifices owing to build-up of solids.…”

“…Hill (1994, 1996) used an eluent containing water and acetonitrile for the speciation of metabolites of satraplatin. To allow a gradient elution with acetonitrile concentrations up to 95%, an interface was developed to desolvate the HPLC eluent prior to introduction to the plasma (Cairns, Ebdon, & Hill, 1996). The interface consisted of a common concentric nebuliser, a heated spray chamber, a membrane desolvator, and a condenser.…”

Trace Metal Speciation with ICP‐MS Detection

“…The addition of small quantities of organic solvent also has the advantage of increasing analyte signals for metalloids like As, Se, Sb and Te, as shown in Organic solvents are frequently used in mobile phases to achieve separation with reversed phase HPLC. 116 However, their presence has a number of detrimental effects during detection by ICP-MS. 117,118 High amounts of organic solvents in the mobile phase decrease the sensitivity, and the deposition of carbon on the cones can cause blocking of the sampler and skimmer orifice. Additionally, introduction of organic solvents may extinguish the plasma or cause plasma instability.…”

“…Adding a small amount of oxygen to the nebuliser gas flow and operating the plasma at higher powers can also help. 117 …”

“…This reference material contains MeHg highly enriched in 200 Hg and comes as a 34.5 mg/L solution with the concentration certified for at least 2 years when stored at −20 • C. Recently, the high-yield synthesis of 198 Hg-labelled MeHg has also been realised. 290 DBT and TBT enriched in 117 Sn have been produced by the Laboratory of the Government Chemist (LGC, UK), but are not yet available on the market. Mostly, isotopically enriched standards are fabricated in-house.…”