Analysis of free cisplatin in microdialysates and plasma ultrafiltrate by liquid chromatography-tandem mass spectrometry.

Cisplatin is a potent cytotoxic agent used in the treatment of various malignancies and exerts its antitumor effect through malignant cell DNA damage and apoptosis induction. Evaluation of systemic delivery of cisplatin is important in optimization of cisplatin treatment. However, accurate quantification of systemic cisplatin is challenging due to its various forms in circulation. This study aimed to develop a sensitive (LOQ < 0.1 µg/mL) and precise Ultra Performance Liquid Chromatography (UPLC) - Tandem Mass Spectrometry (MS/MS) method for quantifying free cisplatin in microdialysates and plasma. Furthermore the aim was to compare free cisplatin concentrations measured in standard plasma samples with those obtained from intravenous microdialysis catheters in a porcine model. The method developed utilizes dichloro(ethylenediamine)platinum(II) as an internal standard that co-elutes with cisplatin, ensuring precise correction for ion suppression/enhancement effects. The method was validated, demonstrating linearity up to 100 µg/mL and good intermediate precision (CV% < 6 %) in the range of 1.0-100 µg/mL, with an LOQ of 0.03 µg/mL. The pharmacokinetic parameters (AUC0-last, Cmax, T1/2, and Tmax) showed no significant differences between the two sampling methods. This validated LC-MS/MS method provides a reliable tool for quantifying systemic free cisplatin concentrations, facilitating future systemic and local pharmacokinetic evaluations for optimization of cisplatin-based cancer treatments.

A small suberythemal ultraviolet B dose every second week is sufficient to maintain summer vitamin D levels: a randomized controlled trial.

BACKGROUND: It is known that ultraviolet (UV) B radiation increases serum 25-hydroxyvitamin D(3) [25(OH)D] level. However, there is uncertainty about the relationship between the maintenance of vitamin D status and UVB. OBJECTIVES: To define the frequency of UVB exposure necessary for maintaining summer 25(OH)D levels during the winter. METHODS: In total, 60 participants were included from October 2008 to February 2009 (16weeks) and randomized for UVB exposure of 1 standard erythema dose (SED) to ∼88% body area once a week (n=15 completed), every second week (n=14 completed) or every fourth week (n=12 completed). The controls (n=14 completed) had no intervention. Vitamin D was measured at baseline, every fourth week before exposure, and 2days after the last UVB exposure. RESULTS: The 25(OH)D levels (mean) after UVB exposure once a week increased significantly (from 71·9 to 84·5nmolL(-1) ) (P<0·0001), whereas UVB exposure every second week maintained 25(OH)D levels (P=0·16). A significant decrease in mean 25(OH)D levels (from 56·4 to 47·8nmolL(-1) ) (P<0·0001) was found after UVB exposure once every fourth week and for the control group (from 64·8 to 40·1nmolL(-1) ) (P<0·0001). The development in 25(OH)D levels during the 16-week study period were negatively correlated with baseline 25(OH)D (P<0·0001). Further, the increase in 25(OH)D after the last UVB exposure was negatively correlated with the 25(OH)D level just before the last UVB exposure (P<0·0001). CONCLUSIONS: Exposure to a UVB dose of 1 SED every second week to ∼88% body area is sufficient for maintaining summer 25(OH)D levels during the winter.

Interdependence between body surface area and ultraviolet B dose in vitamin D production: a randomized controlled trial.

BACKGROUND: Ultraviolet (UV) B radiation increases serum vitamin D level expressed as 25-hydroxyvitamin-D(3) [25(OH)D], but the relationship to body surface area and UVB dose needs investigation. OBJECTIVE: To investigate the importance of body surface area and UVB dose on vitamin D production after UVB exposure. METHODS: We randomized 92 participants to have 6%, 12% or 24% of their skin exposed to 0·75 (7·5 mJ cm(-2) at 298 nm using the CIE erythema action spectrum), 1·5 (15 mJ cm(-2) ) or 3·0 (30 mJ cm(-2) ) standard erythema doses (SED) of UVB. Each participant underwent four UVB exposures at intervals of 2-3 days. Skin pigmentation and 25(OH)D levels were measured before and 48 h after the final exposure. RESULTS: The increase in 25(OH)D after irradiation [Δ25(OH)D] was positively correlated with body surface area (P = 0·006; R(2) = 0·08) and UVB dose (P < 0·0001; R(2) = 0·28), and negatively correlated with baseline 25(OH)D (P < 0·0001; R(2) = 0·18), for the entire data sample. However, when analysing each body surface area separately, we found a significant UVB response correlation for 6% (P < 0·0001; R(2) = 0·48) and 12% (P = 0·0004; R(2) = 0·35), but not for 24%. We also found a significant skin area response correlation for 0·75 SED (P < 0·0001; R(2) = 0·56), but not for 1·5 and 3·0 SED when analysing each UVB dose separately. The relationships did not change significantly after adjustment of Δ25(OH)D for baseline 25(OH)D. CONCLUSION: The increase in 25(OH)D depends mainly on the UVB dose; however, for small UVB doses the area of irradiated body surface is important.