Aluminum and other chemical elements in parenteral nutrition components and all-in-one admixtures.

BACKGROUND & AIMS: Parenteral nutrition (PN) can lead to high or even toxic exposure to aluminum (Al). We aimed to quantify concentrations of Al and other chemical elements of all-in-one (AIO) PN admixtures for adults prepared from commercial multichamber bags (Olimel® 5.7%, Omegaflex® special, SmofKabiven®, all with and without electrolytes) and vitamin and trace element additives over a 48-h period. Secondly, we determined the level of Al contamination resulting from admixing and infusion set use. METHODS: We used dynamic reaction cell and kinetic energy discrimination inductively coupled plasma mass spectrometry (ICP-MS) to quantify Al, arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), molybdenum (Mo), nickel (Ni), antimony (Sb), selenium (Se), tin (Sn), vanadium (V), and zinc (Zn) in AIO PN admixtures. We extracted samples for analysis via the bag injection ports and infusion sets over a 48-h period after admixing. We compared the measured Al concentrations of AIO PN admixtures with calculated values based on the measured concentrations of individual chamber contents and additives. RESULTS: Mean (standard deviation) baseline Al concentrations in AIO PN admixtures ranged from 10.5 (0.5) to 59.3 (11.4) µg/L and decreased slightly over the 48 h (estimate [standard error] -0.09 [0.02] µg/L/hour, p <0.001). Thus, certain products exceeded the widely accepted limit of 25 µg/L. There was no significant difference in Al concentrations between samples extracted via the bag injection ports or infusion sets (p = 0.33), nor between measured and calculated Al concentrations of AIO PN admixtures (p = 0.91). CONCLUSION: Because certain commercially available PN admixtures for adults proved to contain excessively high levels of Al in our study, regulations and corresponding quality requirements at the authority level (e.g., Pharmacopoeia and regulatory authorities) are urgently required. Our results showed that the PN handling process (admixing and supplementing additives) or the materials of the infusion set did not lead to additional Al contamination to any extent. Moreover, calculated Al concentrations of AIO PN admixtures derived from individual chamber contents and additives are valid.

Physicochemical Stability and Compatibility Testing of Voriconazole in All-in-One Parenteral Nutrition Admixtures.

(1) Drug compatibility with all-in-one (AiO) parenteral nutrition (PN) admixtures is a very important pharmaceutical quality issue to be answered based on appropriate laboratory testing. We assessed voriconazole (V), a poorly water-soluble (logP ≈ 1) single-daily dosed antifungal drug monitored in patients and thus candidate for AiO PN admixing for convenient and safe patient care. We evaluated V compatibility and stability in AiO PN admixtures through adapted therapeutic drug monitoring method (drug stability) and visual microscopic emulsion stability by lipid droplets analysis improved by an automated microscopic digital assessment. (2) V was added in concentrations of 0.05/0.25/0.5 mg/mL (143.1/715.7/1431.5 µM), correlating to daily therapeutic dosing, to three commercially available industrial AiO PN admixtures. Three aliquots were stored in the refrigerator (4 °C), at room temperature (24 °C) and under stress conditions in a water bath (37 °C). Samples taken at 0/24/48/72/168 h after admixing were subjected to a stability-indicating one-week analysis. Assessment included visual examination, lipid droplet measurement according to an established and validated method (bright-field microscopy using oil immersion), pH measurement (glass electrode) and V identification/quantification (LC-MS/MS). (3) After one week, all samples at 37 °C showed slight yellow discoloration. The pH values remained stable. All samples met specifications for lipid droplets according to size (upper size ≤8 µm, mean size <4.5 ± 2 µm) and number (n ≤ 9 lipid droplets >5 µm). V concentrations were within an acceptable range, calculated for every timepoint as percent of the theoretical concentration spiked into the AiO PN. The median recovery was 98.2% (min-max, 90-112%). (4) At therapeutic doses, commercial V formulations were compatible and stable within specifications over one week in commonly used volumes of commercial AiO PN admixtures at 4-37 °C.

Simultaneous determination of levodopa and 3-O-methyldopa in human plasma by liquid chromatography with electrochemical detection.

A simple and rapid assay is described for the simultaneous analysis of levodopa (l-DOPA) and 3-O-methyldopa (3-OMD) in human plasma samples, applying an ion-pair reversed-phase liquid chromatographic method with electrochemical detection, designed for clinical trials performed to study the effect of peripheral catechol-O-methyltransferase inhibitors on the metabolism of l-DOPA. After protein precipitation of 100 microl plasma sample aliquots with perchloric acid, the analytes are directly injected, separated within 10 min and simultaneously quantified down to 20 ng/ml by an electrochemical detector equipped with a dual-electrode system operating in redox mode eliminating effectively potential endogenous and exogenous interferences. The intra-assay precision for l-DOPA and 3-OMD was 1.34-6.54 and 3.90-5.50%, whereas the inter-assay precision was 2.09-7.69 and 4.16-9.90%, respectively. The recoveries were close to 90% for l-DOPA and almost 100% for 3-OMD. Satisfactory storage stability was achieved for up to 16 weeks at -70 degrees C by stabilizing plasma samples with antioxidants.