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Nutr J. 2016 Mar 22;15:29. doi: 10.1186/s12937-016-0149-x.

Development and evaluation of a test program for Y-site compatibility testing of total parenteral nutrition and intravenous drugs.

Author information

Hospital Pharmacy of North Norway Trust, Tromsø, Norway.
Department of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
Department for Medicinal Product Assessment, Norwegian Medicines Agency, Oslo, Norway.
Hospital Pharmacy, Haukeland University Hospital, Bergen, Norway.
Norwegian Medicines for Children Network, Bergen, Norway.
Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
Department of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
School of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.



There is no standardized procedure or consensus to which tests should be performed to judge compatibility/incompatibility of intravenous drugs. The purpose of this study was to establish and evaluate a test program of methods suitable for detection of physical incompatibility in Y-site administration of total parenteral nutrition (TPN) and drugs.


Eight frequently used methods (dynamic light scattering, laser diffraction, light obscuration, turbidimetry, zeta potential, light microscopy, pH-measurements and visual examination using Tyndall beams), were scrutinized to elucidate strengths and weaknesses for compatibility testing. The responses of the methods were tested with samples containing precipitation of calcium phosphate and with heat destabilized TPN emulsions. A selection of drugs (acyclovir, ampicillin, ondansetron and paracetamol) was mixed with 3-in-1 TPN admixtures (Olimel® N5E, Kabiven® and SmofKabiven®) to assess compatibility (i.e. potential precipitates and emulsion stability). The obtained compatibility data was interpreted according to theory and compared to existing compatibility literature to further check the validity of the methods.


Light obscuration together with turbidimetry, visual inspection and pH-measurements were able to capture signs of precipitations. For the analysis of emulsion stability, light obscuration and estimation of percent droplets above 5 μm (PFAT5) seemed to be the most sensitive method; however laser diffraction and monitoring changes in pH might be a useful support. Samples should always be compared to unmixed controls to reveal changes induced by the mixing. General acceptance criteria are difficult to define, although some limits are suggested based on current experience. The experimental compatibility data was supported by scattered reports in literature, further confirming the suitability of the test program. However, conflicting data are common, which complicates the comparison to existing literature.


Testing of these complex blends should be based on a combination of several methods and accompanied by theoretical considerations.


Emulsion stability; Incompatibility; Light obscuration; Oil droplet size; Parallel infusion; Particle content; Particle size; Precipitation; Turbidity; Zeta potential

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