Stability of caffeine citrate intravenous dilutions in sodium chloride and glucose solutions

Caffeine citrate, a methylxanthine derivative, is commonly used in the management of apnoea of prematurity. In clinical settings, particularly in neonatal intensive care units, various dilutions of caffeine citrate in intravenous fluids are required to ensure precise and individualised dosing for extremely low birth weight infants. This study aimed to assess the stability of caffeine citrate solutions at concentrations of 1 mg/mL and 12.5 mg/mL in 0.9% w/v sodium chloride and 5% w/v glucose, stored at room temperature and under refrigeration up to 48 hours.

Caffeine citrate concentrations were measured using a high-performance liquid chromatography method with ultraviolet detection (HPLC-UV). Solutions were stored at room temperature (22°C) and at 8°C for up to 48 hours. Two solvents for caffeine citrate were studied: normal saline (0.9% w/v sodium chloride), and 5% w/v glucose. The calibration curves of the HPLC-UV method were linear over the range of 0.1-12.5 mg/mL for both types of intravenous fluid. The stability criterion was defined according to International Council for Harmonisation (ICH) M10 (±15% of nominal concentration), and compliance with the stricter United States Pharmacopeia (USP) criterion (±10%) was also assessed.

All samples remained within the ICH M10 acceptance limits. Most results also complied with the USP±10% threshold; however, three values (12.5 mg/mL in 0.9% w/v sodium chloride at 24 hours refrigerated, and 1 mg/mL in 5% w/v glucose at 24 hours and 48 hours refrigerated) exceeded 110% (112.9%, 111.3%, and 111.4%, respectively).

Caffeine citrate diluted in 0.9% w/v sodium chloride or 5% w/v glucose is chemically stable at concentrations of 1 mg/mL and 12.5 mg/mL for up to 48 hours when stored at room temperature, meeting ICH and USP acceptance criteria in all cases. Caffeine citrate solutions did not meet the USP±10% criterion if stored at 8°C for 24 hours.