Evaluation of reprotoxic risk assessment in a control laboratory (CL): choice of a new method for the calcium dosage in parenteral nutrition preparation
4 October 2018L. Favrelle1 ; AF. Dumas1 ; J. Leenhardt1 ; M. Durand1 ; B. Allenet1,2 ; P. Bedouch1 ; MD. Desruet1 ; R. Mazet1,3 1 Pharmacie centrale, Centre Hospitalo-Universitaire Grenoble Alpes,
2 ThEMAS,TIMC-IMAG UMR CNRS 5525, Université Grenoble Alpes,
3 DPM, UMR CNRS 5063, ICMG FR 2607, Université Grenoble Alpes
A chemical risk assessment in the CL identified 30 carcinogenic, mutagenic or reprotoxic (CMR) substance, including imidazole, a 1A reprotoxic molecule. It is present in the Arsenazo III (A3) method (Biolabo®) and used daily for the determination of calcium in parenteral nutrition preparations. This work aims to substitute this method with a constant cost (0.26 € / dosage), while ensuring the quality of results and the worker safety.
Material and method
An evaluation of the different available UV-Visible spectrophotometric methods of calcium determination was realized. The choice among the different methods was made according to the following criteria:
i) No chemical risk for the manipulator,
ii) Constant cost and time handling (30 minutes for 10 samples),
iii) Method validated according to the recommendations of the International Harmonization Conference (linearity over 5 points range repeated 3 days , reproducibility, accuracy, fidelity on 1 point of range repeated 6 times 3 consecutive days, no matrix effect), iiii) Time stability of the colorimetric reaction. 
There are 3 methods for determining calcium by UV-Visible spectrophotometry. Among them, 6 kits are available but 3 were excluded for safety and time handling reasons and only one kit meets all of our 3 criteria : A3 kit (Randox®). It is linear over a range of 0 to 3.59 mmol/L (r²> 0.999), faithful (coefficient of variation (CV) <2%) and accurate (CV <5%). No matrix effects occurs with lipids present in industrial parenteral nutrition most currently used for paediatrics (Numetah® G13 and G16 G19), α = 5%. The colorimetric reaction is stable over 120 min.
The A3 assay kit (Randox®) is the only one available method that meets all criteria. This is a colorimetric method of calcium Arsenazo III, free from reprotoxic substance. It is easy to handle (30 minutes for 10 samples, stable enough time), and even cheaper than the kit previously used (0.21 € / dosage). No matrix effects is interfering with Numetah® G13and G16. This approach is a first step towards the systematic reduction of the chemical risk in the CL.
 Q2(R1) : Validation of Analytical Procedures, International Harmonization Conference 2015