Stability of prostaglandin E1 solutions stored in polypropylene syringes for continuous intravenous administration to newborns

Abstract

Objective: We aimed to monitor the physicochemical stability of prostaglandin E₁ (PGE₁) 1.5 and 15 µg/mL in 10% dextrose stored in polypropylene syringes.

Methods: We developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method to detect and quantify levels of PGE₁. Method selectivity was performed with a mixture of PGE₁ and its degradation products. Forced degradation tests were performed to determine which degradation products were most likely to form. PGE₁ injection solutions in 10% dextrose were stored in unprotected and shielded-from-light polypropylene syringes in a climatic chamber. Samples were taken immediately after preparation (T₀) and after 24, 48, 72 and 168 hours for analysis. PGE₁ solutions were considered stable if ≥90.0% of the initial concentration was retained.

Results: The LC-HRMS method was validated in the range of 0.086-0.200µg/mL PGE₁ with trueness values between 98.2% and 100.3%, and repeatability and intermediate precision values of <2.2%and <4.7%, respectively. The quantification and detection limits of the method were 0.086 and 0.026µg/mL, respectively. PGE₁ and its degradation products were resolved chromatographically. PGE₁ injection solutions were≥90.0%stable after 48hours in unprotected from light (UPL) syringes. The solutions remained clear without precipitation, colour or pH modification and subvisible particles within the permitted levels. Prostaglandin A₁ was the sole degradation product observed.

Conclusions: A LC-HRMS method to evaluate PGE₁ stability in a 10% dextrose was developed and validated. PGE₁ 1.5 and 15µg/mL in 10% dextrose solution are stable for 48hours when stored at 30ºC in UPL polypropylene syringes.

Keywords: alprostadil; drug stability; intensive care unit; liquid chromatography; mass spectrometry; neonatal; newborn; prostaglandins E.

Figure 1

Chemical structures of prostaglandin E₁ degradation products observed in accelerated degradation studies.

Figure 2

Prostaglandin E₁(PGE₁) accelerated degradation assay. (A) PGE₁ in 10% dextrose injection solution. (B) Strongly acidic condition (HCl 0.1 M, 25°C). (C) Softly basic condition (NH₄OH 5%, 25°C). (D) Strongly basic condition (NaOH 0.1 M, 25°C). (E) Oxidative condition (H₂O₂ 15%, 25°C). (F) Thermal condition (H₂O, 80°C). (G) Photolytic condition (H₂O, UV-light, 30°C). All treatments were performed for 3 hours.