Stability and Compatibility of an Intramuscular Fetal Anesthetic Cocktail for Fetal Intervention

Abstract

<b><i>Introduction:</i></b> The aim of the study was to evaluate chemical stability and physical compatibility when combining fentanyl, rocuronium, and atropine in a fixed ratio to support intramuscular drug delivery during fetal intervention and surgery. <b><i>Methods:</i></b> A highly concentrated combination of fentanyl, rocuronium, and atropine was created based on common prescribing practices at a maternal-fetal care center. Chemical stability testing was completed using liquid chromatograph mass spectrometry-mass spectrometry (LC/MS-MS) to detect and quantitate atropine, rocuronium, and fentanyl, with fentanyl-d₅ being an internal standard at 6, 12, 24, and 36 h following sample preparation. Physical compatibility testing was completed using United States Pharmacopeia (USP) &lt;788&gt; recommended analytical technique of light obscuration in addition to novel backgrounded membrane imaging at 6 and 24 h following sample preparation. Physical compatibility was determined using USP &lt;788&gt; particle count limits for both techniques. <b><i>Results:</i></b> Based on LC/MS-MS results, the samples retained expected medication concentrations at all time points tested. For physical compatibility testing, the particle counts met criteria to be considered compatible per USP &lt;788&gt; large-volume particle count thresholds at 6 h by both methods but exceeded tolerable thresholds at 24 h. <b><i>Discussion/Conclusion:</i></b> The combination of rocuronium, fentanyl, and atropine for intramuscular fetal administration is physically compatible and chemically stable for 6 h.