Analysis of all-in-one parenteral nutrition admixtures by liquid chromatography and laser diffraction: study of stability.

Abstract

All-in-one parenteral nutrition admixtures are complex lipid emulsions (oil/water) which require absolute sterility, stability and no precipitates. Particle diameter must be in the range 0.4--1 microm in order to mime the size of chylomicra. Added vitamins must not degrade during infusion time (24 h). In this study, the physicochemical stability of parenteral nutrition admixtures was tested in the course of time at different storage temperatures. Two liquid chromatographic methods, based on solid phase extraction (SPE), were developed for fat-soluble vitamin determination. Stability studies were carried out on three industrial lipid emulsions and on six compounded all-in-one admixtures. They were stored at three different temperatures: 4 degrees C (storage), 25 degrees C (compounding) and 37 degrees C (infusion); then they were analyzed at starting time and at 24, 48 and 72 h after compounding. Particle diameter was determined by means of Laser Particle Sizer Analysette 22, which uses laser diffraction technique (light scattering -- reverse Fourier optics). Fat-soluble vitamins (retinol palmitate and alpha-, delta-, gamma-tocopherol) were determined in admixtures with a branded vitamin compound called Idroplurivit Liofilizzato. Samples were extracted by SPE on C(18) cartridges, then they were separated by reversed-phase liquid chromatography (LC) and detected by ultraviolet detection (retinol palmitate) and electrochemical detection (tocopherols). Laser diffraction analysis pointed out that particle size did not change in the course of time at the tested temperatures. LC analysis showed that vitamins interact each other and degrade after compounding at different times and storage temperatures; only retinol palmitate is stable at 37 degrees C. Retinol palmitate recovery was 98%, coefficient of variation (CV) 5.4%, detection limit 25 microg/l, limit of quantitation 75 microg/l and there were not interfering substances. Tocopherols average recovery was 99%, CV 3.5%, detection limit 15 ng/l and limit of quantitation 50 ng/l. In conclusion, all-in-one parenteral admixtures were proved to be physically stable under analysis conditions, but degradation of retinol palmitate and tocopherols requires admixtures with vitamins to be infused within 24 h after compounding.