Stability study of Letermovir in solution in 0.9% NaCl polypropylene bags

4 October 2023

F. Rioblanc, P. Claraz, C. Jadoul, A. Sabri, J. Roupret-Serzec, T. Storme
APHP, Hôpital Robert-Debré, Paris, France

Letermovir (LTR) is a new antiviral used in the prophylaxis of cytomegalovirus infection, from the first days following hematopoietic stem cell transplantation. When the oral route is not suitable for the patient (chemotherapy-induced inflammatory lesions of the digestive mucosa), LTR is administered parenterally for several days or even weeks. The aim of this study is to assess the stability of LTR injectable in 0.9% NaCl bags, to optimize the production of injectable doses and the per os relay, particularly when a magistral preparation is required in pediatrics.

Material & method
Determination is performed by HPLC-DAD equipped with a C18 column heated at 30°C and a mobile phase consisting of ammonium carbonate (1.92 g/L; pH =7.9) at a flow rate of 0.300 mL/min. The HPLC is coupled to a diode array detector. The calibration curve was performed with 3 calibration standards at 25, 50 and 75 µg/mL. The method was validated in accordance with GERPAC recommendations. Forced degradation tests using UV, HCl, NaOH and H2O2 were carried out. LTR stability was studied after dilution of the injectable drug (480mg/24mL) in 0.9% NaCl polypropylene bags. Three concentrations (1, 1.5 and 2 mg/mL) were studied, each in triplicate. The bags were packed in a UV-protective transparent overwrap and left at room temperature. Determination of LTR concentration, testing for degradation products and visual inspection of the bags (particles, color change) were carried out at D0, D1, D3, D7, D15, D22 and D30.

The method is specific, linear, accurate and repeatable. The retention time of LTR is 3.7 min. Forced degradation tests showed that LTR is sensitive to UV and oxidation. For each concentration and up to D30, the LTR concentration deviation was less than 5% from the initial concentration. No degradation products were detected over the study period. No change in color or particles was detected on visual inspection of the pouches.

At room temperature and protected from UV light, LTR diluted to a concentration between 1 mg/mL and 2 mg/mL in a 0.9% NaCl polypropylene bag is stable for 30 days.

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