Exploring the Suitability of High-Performance Thin-Layer Chromatography for the Analysis of Drug Admixtures in Total Parenteral Nutrition Using Caffeine, Ibuprofen and Midazolam as Model Drugs

Total parenteral nutrition (TPN) is a nutritional therapy in children when oral or enteral feeding is not possible, fails to meet nutritional requirements or is contraindicated due to underlying clinical conditions. There are many cases where children who are given one or more than one intravenous medication also need TPN. In order to minimise vein access, these medications are commonly administered via a Y-site IV connection where they admix with TPN, implying a need for compatibility studies before admixing the medication into the nutritional fluid. In this study, previously developed and validated HPTLC methods were verified for their suitability to evaluate the concentrations of three commonly used medications in neonatal intensive care units (NICUs), namely caffeine citrate, ibuprofen arginine, and midazolam hydrochloride. Silica gel 60 F254 HPTLC plates were used as the stationary phase, and acetone: toluene: chloroform (4:3:3, v/v/v), toluene: methanol: ethyl acetate: glacial acetic acid (5.5:3.2:1:0.3, v/v/v/v), and cyclohexane: toluene: diethylamine (7:1.5:1.5, v/v/v) with one drop of 25% ammonia solution were used as mobile phases. The compatibility of the three drugs in their respective TPN admixtures was then assessed at various time points over a 24 h period using these HPTLC methods. Each drug admixed in TPN was directly applied onto the HPTLC plates without further sample pre-treatment. Paired Two-One-Sided Test (TOST) equivalent testing revealed that the concentrations of the selected drugs in TPN were unchanged over the monitoring period (p > 0.05), confirming chemical compatibility. These findings were in line with previous studies that concluded compatibility and reported similar RF and LOD/LOQ values (1.95/5.90 ng/band for caffeine, 252.22/764.30 ng/band for ibuprofen and 10.82/32.78 ng/band for midazolam; R2 ≥ 0.99). As no additional sample pre-treatment was required, HPTLC-based compatibility studies of drug–TPN admixtures may simplify the analytical workflow, making them a cost-effective and time-efficient approach to compatibility testing.