A Reliable HPLC Method for Monitoring Midazolam Plasma Levels in Critically Ill Pediatric Patients

Introduction: Until date, the methods employed in the quantification of midazolam during sedation and in pre-anesthetic patients are somewhat complex and costly. Hence, the development of simple, practical, precise and reliable method becomes extremely important to measure plasma midazolam levels that could allow its monitoring during sedation, especially in patients who need higher doses of midazolam to achieve deep sedation, a situation which is usually fraught with the risk of increase drug levels and toxicity. Objective: The aim of the present study was to develop a simple and reliable method to monitor plasma levels of midazolam in critically ill pediatric patients. Methods: The plasma levels of midazolam were monitored with 200 μl of plasma during infusion in pediatric patients from Intensive Care Unit using a Pursuit C18 column and UV detection of 220 nm. Results: A linearity ranged between 10-10000 ng/ml of midazolam was obtained with a correlation coefficient of 0.999. The inter and intra-day variation had less than 4% of a coefficient of variation and a mean recovery rate of 99%. Monitoring was carried out in 13 children (from 1-17 years old) at 1, 12 and 24 h post-dose and the median values reached were 437.2, 1908.3 and 4077.6 ng/ml, respectively. It is worth mentioning that some patients received doses 4 times greater than the recommended dose. Conclusion: A simple and reliable HPLC method was developed to monitor midazolam levels in critically ill pediatric patients.