Co-administration of Intravenous Drugs: Rapidly Troubleshooting the Solid Form Composition of a Precipitate in a Multi-drug Mixture Using On-Site Raman Spectroscopy

Intravenous drugs are often co-administrated in the sameintravenouscatheter line due to which compatibility issues, such as complex precipitationprocesses in the catheter line, may occur. A well-known example thatled to several neonatal deaths is the precipitation due to co-administrationof ceftriaxone- and calcium-containing solutions. The current studyis exploring the applicability of Raman spectroscopy for testing intravenousdrug compatibility in hospital settings. The precipitation of ceftriaxonecalcium was used as a model system and explored in several multi-drugmixtures containing both structurally similar and clinically relevantdrugs for co-infusion. Equal molar concentrations of solutions containingceftriaxone and calcium chloride dihydrate were mixed with solutionsof cefotaxime, ampicillin, paracetamol, and metoclopramide. The precipitateformed was collected as an unknown material, dried,and analyzed. Several solid-state analytical methods, including X-raypowder diffraction, Raman spectroscopy, and thermogravimetric analysis,were used to characterize the precipitate. Raman microscopy was usedto investigate the identity of single sub-visual particles precipitatedfrom a mixture of ceftriaxone, cefotaxime, and calcium chloride. X-raypowder diffraction suggested that the precipitate was partially crystalline;however, the identity of the solid form of the precipitate could notbe confirmed with this standard method. Raman spectroscopy combinedwith multi-variate analyses (principal component analysis and softindependent modelling class analogy) enabled the correct detectionand identification of the precipitate as ceftriaxone calcium. Ramanmicroscopy enabled the identification of ceftriaxone calcium singleparticles of sub-visual size (around 25 mu m), which is in thesize range that may occlude capillaries. This study indicates thatRaman spectroscopy is a promising approach for supporting clinicaldecisions and especially for compatibility assessments of drug infusionsin hospital settings.

Automated summary

This study explores the applicability of Raman spectroscopy for testing intravenous drug compatibility in hospital settings. The researchers found that Raman spectroscopy combined with multivariate analysis can accurately detect and identify precipitates. The study suggests that Raman spectroscopy is a promising method for supporting clinical decisions and assessing drug compatibility in hospital settings.