Intravenous drugs are often co-administrated in the same
intravenous
catheter line due to which compatibility issues, such as complex precipitation
processes in the catheter line, may occur. A well-known example that
led to several neonatal deaths is the precipitation due to co-administration
of ceftriaxone- and calcium-containing solutions. The current study
is exploring the applicability of Raman spectroscopy for testing intravenous
drug compatibility in hospital settings. The precipitation of ceftriaxone
calcium was used as a model system and explored in several multi-drug
mixtures containing both structurally similar and clinically relevant
drugs for co-infusion. Equal molar concentrations of solutions containing
ceftriaxone and calcium chloride dihydrate were mixed with solutions
of cefotaxime, ampicillin, paracetamol, and metoclopramide. The precipitate
formed was collected as an “unknown” material, dried,
and analyzed. Several solid-state analytical methods, including X-ray
powder diffraction, Raman spectroscopy, and thermogravimetric analysis,
were used to characterize the precipitate. Raman microscopy was used
to investigate the identity of single sub-visual particles precipitated
from a mixture of ceftriaxone, cefotaxime, and calcium chloride. X-ray
powder diffraction suggested that the precipitate was partially crystalline;
however, the identity of the solid form of the precipitate could not
be confirmed with this standard method. Raman spectroscopy combined
with multi-variate analyses (principal component analysis and soft
independent modelling class analogy) enabled the correct detection
and identification of the precipitate as ceftriaxone calcium. Raman
microscopy enabled the identification of ceftriaxone calcium single
particles of sub-visual size (around 25 μm), which is in the
size range that may occlude capillaries. This study indicates that
Raman spectroscopy is a promising approach for supporting clinical
decisions and especially for compatibility assessments of drug infusions
in hospital settings.