Determination of Propylene Glycol in Low Volume Plasma and Urine Samples of Neonates by LC with Photodiode Array Detection

Abstract

In order to enhance the sensitivity and to develop a method suitable for quantification of propylene glycol (PG) in low volume neonate plasma and urine samples, several steps in earlier described high performance liquid chromatographic methods were optimised. Chromatographic separation on a reversed-phase column and ultraviolet detection resulted in cleaner chromatograms without interfering compounds. Linearity of the standard curves was validated in the concentration range 0.25-50 mg L -1 . The lower limit of quantification was 20 times lower than in earlier described methods. Presented method was suitable for quantification of PG concentrations in low volume neonate plasma (15-46 mg L -1 ) and urine samples (20-175 mg L -1 ) enabling us to document very low renal versus non-renal contribution of PG clearance in neonates.

The propylene glycol research project to illustrate the feasibility and difficulties to study toxicokinetics in neonates

“…Since PG is eliminated by hepatic (alcohol dehydrogenase) metabolism and primary renal elimination, we aimed to quantify PG in low volume plasma and urine samples. To illustrate the feasibility, PG time-concentration plasma observations as collected in neonates following iv paracetamol loading dose (20 mg/kg, equal to 16 mg/kg PG, PARANEO study) administration are provided Kulo et al, 2011). Based on 69 PG plasma measurements following 16 mg/kg PG administration, peak PG concentrations were about 40 mg/L, through concentration 6 h later were 20-30 mg/L.…”

“…In a second step, a PG assay was developed (Kulo et al, 2011). Neonates display extensive variability in metabolic and renal elimination clearance (Allegaert et al, 2008).…”

Biochemical tolerance during low dose propylene glycol exposure in neonates: A formulation-controlled evaluation

“…The group of MacDonald estimated a PG serum elimination half life in preterm neonates (all < 1.5 kg) to be 10.8 to 30.5 h [8,9]. To compare observations in preterm neonates with more mature neonates, we recalculated PG pharmacokinetics in a dataset of 22 PG plasma (median PG concentration 31.9, range 15–46 mg/l) samples collected in a cohort of 6 (near)term neonates (median weight 3.08 kg, median postmenstrual age 38 weeks) [16]. Assuming a one compartment model, with zero order input and first order output, the calculated PG elimination half life is 8.88 h, PG clearance is 0.0683 l/h.…”

Low but Inducible Contribution of Renal Elimination to Clearance of Propylene Glycol in Preterm and Term Neonates

“…PG was determined in low volume neonate plasma (15-46 mg/L) and urine (20-175 mg/L) by means of highperformance liquid chromatography with photodiode array detection as described by Kulo et al 16 The method was validated in the concentration range of 0.25-50 mg/L. 16 Samples with concentrations higher than the validation range were reanalyzed after appropriate dilution until they fell into the validation range.…”