Element response variations under different laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) operating conditions were investigated to identify important factors for selecting an internal standard (IS) for quantitative elemental bio-imaging. Analytes covering a range of atomic masses and first ionisation potentials (FIP) were selected to investigate the signal response variation with changes in laser spot diameter, mass bias and cell sampling position. In all cases, an IS improved experimental precision regardless of a close match in element mass or FIP but optimal analyte/IS combinations depended on the difference in masses of the analyte and IS. Particular attention was paid to ¹³C as this isotope is typically used as an IS in elemental bio-imaging applications. Despite its non-ideal IS characteristics (often different mass and FIP to many analytes), possibility of abundance sensitivity effects and poor signal-to-background ratio, ¹³C was a suitable IS candidate exhibiting a linear response with respect to the mass ablated, apparent independence from the high abundance of the adjacent ¹⁴N mass peak and effective analyte normalisation after background subtraction as long as the ¹³C signal from the sample was at least 6% of the gross signal.

A method for quantitative analysis of biological soft tissues by laser ablation-inductively coupled plasma-mass spectrometry has been developed. Polymer film standards were produced by spin coating spiked solutions of polymethylmethacrylate onto quartz substrates. Calibration curves throughout the range of 0–400 μg g⁻¹ yielded correlation coefficients better than 0.999 for ⁶⁶Zn and ⁶³Cu. Spiked, homogenised soft tissue standards were quantified by LA-ICP-MS against the thin film standards. The results agreed with values calculated from solution nebulisation ICP-MS. A procedure for internal standardisation by employing ruthenium or yttrium in the underlying thin film was also assessed.

Solute carrier (SLC) transporters regulate the cellular influx and disposition of endogenous and xenobiotic compounds, including anticancer agents such as the multikinase inhibitors (MKIs). Recent evidence suggests that MKIs may also inhibit SLC-dependent transport of coadministered drugs, although present information on the relative susceptibilities of multiple SLC transporters is limited. This study evaluated 18 MKI drugs and metabolites as inhibitors of prototypic substrate uptake by 13 SLC transporters that were overexpressed in human embryonic kidney cells. Organic anion transporting polypeptides (OATPs) 1A2, 1B3, and 2B1, organic anion transporter 3 (OAT3), and organic cation transporter 1 (OCT1) were inhibited by most MKIs, whereas substrate uptake by OATP1B1, OAT1, 2, and 4, OCT2 and 3, and organic zwitterion/cation transporter 1 (OCTN1) was less susceptible to inhibition; OCTN2 was also inhibited by cediranib. In further studies, IC₅₀ values were determined for the most effective MKIs, and erlotinib and cediranib were found to be potent competitive inhibitors of OATP2B1 (K_i = 41 nM) and OATP1A2 (K_i = 33 nM), respectively. From predictive approaches, several MKI-SLC interactions were found to be of potential in vivo significance.