Laser ablation-inductively coupled plasma-mass spectrometry analysis reveals differences in chemotherapeutic drug distribution in surgically resected pleural mesothelioma.

AIMS: Pleural mesothelioma (PM) is a highly aggressive thoracic tumour with poor prognosis. Although reduced tissue drug accumulation is one of the key features of platinum (Pt) resistance, little is known about Pt distribution in human PM. METHODS: We assessed Pt levels of blood samples and surgically resected specimens from 25 PM patients who had received neoadjuvant Pt-based chemotherapy (CHT). Pt levels and tissue distributions were measured by laser ablation-inductively coupled plasma-mass spectrometry and correlated with clinicopathological features. RESULTS: In surgically resected PM specimens, mean Pt levels of nontumourous (fibrotic) areas were significantly higher (vs tumourous regions, P = 0.0031). No major heterogeneity of Pt distribution was seen within the tumourous areas. Pt levels correlated neither with the microvessel area nor with apoptosis rate in the tumourous or nontumourous regions. A significant positive correlation was found between serum and both full tissue section and tumourous area mean Pt levels (r = 0.532, P = 0.006, 95% confidence interval [95% CI] 0.161-0.771 and r = 0.415, P = 0.039, 95% CI 0.011-0.702, respectively). Furthermore, a significant negative correlation was detected between serum Pt concentrations and elapsed time from the last cycle of CHT (r = -0.474, P = 0.017, 95% CI -0.738--0.084). Serum Pt levels correlated negatively with overall survival (OS) (P = 0.029). CONCLUSIONS: There are major differences in drug distribution between tumourous and nontumourous areas of PM specimens. Serum Pt levels significantly correlate with full section and tumourous area average Pt levels, elapsed time from the last CHT cycle, and OS. Further studies investigating clinicopathological factors that modulate tissue Pt concentration and distribution are warranted.

Extraction and pre-concentration of platinum and palladium from microwave-digested road dust via ion exchanging mesoporous silica microparticles prior to their quantification by quadrupole ICP-MS.

We report on the use of mesoporous silica microparticles (µPs) functionalized with quarternary amino groups for the isolation of platinum and palladium tetrachloro complexes from aqueous road dust digests. The µPs have a size ranging from 450 to 850 nm and are suspended directly in the aqueous digests, upon which the anionic Pt and Pd complexes are retained on the cationic surface. Subsequently, the µPs are separated by centrifugation. Elements that cause spectral interferences in ICP-MS determination of Pt and Pd can be quantitatively removed by adding fresh 0.240 mol L-1 HCl to the µPs and by repeating the centrifugation step. The analyte-loaded µPs are then dissolved in 0.1 mL of 2 mol L-1 HF, diluted to 2 mL, and the solutions thus obtained are analyzed by quadrupole ICP-MS. This method avoids analyte elution from the sorbent. This "dispersed particle extraction" approach yielded a run-to-run relative standard deviation ≤ 5 % for Pt and ≤ 4 % for Pd (at 0.1 ng mL-1, n = 4 road dust digests). Method detection limits (expressed as concentrations in the dust samples) are 2 and 1 ng g-1 for Pt and Pd, respectively. The method was validated by analysis of a reference material (BCR CRM 723) and applied to the analysis of road dust samples collected in downtown Vienna. Pt and Pd concentrations in samples collected in summer and in winter were compared, with concentrations ranging from 205 to 1445 ng g-1 for Pt and from 201 to 1230 ng g-1 for Pd. Graphical AbstractMesoporous silica microparticles (µPs) functionalized with quarternary amino groups were used for isolating platinum and palladium from aqueous road dust digests. The µPs were suspended directly in the aqueous digests, and the analyte-loaded µPs were analyzed using "dispersed particle extraction".