Control of a pediatric clonidine solution at 10 µg/mL by capillary electrophoresis

4 October 2023

L. Trocherie, R. Vasquez, M.-N. Guerrault-Moro, A.-C. Lagrave
Centre Hospitalier Intercommunal Poissy-St Germain, France

Clonidine is a drug used for opioid withdrawal syndrome in infants. The aim was to provide a suitable preparation to address the unavailability of a pediatric form. The project was carried out in 3 stages: formulation selection, development of the dosage method, and validation of this method.

Materials and methods
The formulation selection was based on literature analysis, comparing, and selecting the best formulation. The selection criteria included: patient appropriate galenic form, tolerance (pH, osmolarity), absence of excipients with notable effects, ease of preparation and dosage.
The development of analytical control for the preparation was performed by capillary electrophoresis in two steps:
1. Clonidine assay with the addition of a lidocaine internal standard at 10 µg/mL: reverse capillary with an effective length of 8.5 cm, 25°C, -20 kV, wavelength 200 nm, injection pressure -50 mBar for 5 seconds, and phosphate buffer at pH 2.5.
2. Identification of excipients: using a capillary of 56 cm, 25°C, -25 kV, wavelength 350 nm, and reference at 230 nm (in reverse UV), injection pressure 50 mBar for 6 seconds, and buffer at pH 12.1.
The method validation was based on the SFSTP (French Society of Pharmacology and Toxicology) standards, establishing an accuracy profile at three concentrations: 6.3, 9, and 11.7 µg/mL, with acceptable limits defined at +/- 10% and a beta proportion of 95%.

The selected solution consists of potassium sorbate, potassium citrate, citric acid, sodium saccharin, and water.
For clonidine, the obtained results provided an accuracy profile within the established limits, with recovery rates ranging from 96.9% to 98.8%. The coefficients of variation for repeatability were between 2.1% and 2.7%, and for reproducibility were between 2.3% and 3.2%. The analysis time is <3 minutes.
The second method allows the identification of sorbate, saccharin, and citrate (potassium citrate and citric acid) with an analysis time of 7 minutes. The citrate peak corresponds to both potassium citrate and citric acid, but the area under the curve ensures the presence of both components (peak 2 times smaller if one of these excipients is absent).

Capillary electrophoresis allows the control (active ingredient quantification and excipients identification) of a clonidine solution with the addition of only one internal standard. This method offers an alternative to HPLC for the analysis of hospital preparations.
The physicochemical stability is reported to be 3 months according to the literature; however, it will be necessary to demonstrate microbiological stability through a microbial enumeration test.

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