Development and Validation of a Sensitive LC-MS/MS Method for the Determination of D-Serine in Human Plasma

摘要

A validated LC-MS/MS method was developed for the determination of D-Serine in human plasma. The method was fully validated for use with human plasma samples and was linear from 0.19 nmol/ml to 25 nmol/ml. The coefficient of variation was ≤ 5% for the high QC standards and ≤ 8% for the low QC standards in plasma. D-Serine and L-Serine were resolved by pre-column derivatization using (R)-1-Boc-2-piperidine carbonyl chloride as the derivatizating agent. The method was used to determine the concentration of D-Serine in plasma samples obtained in patients receiving a continuous 5-day intravenous infusion of (R,S)-ketamine. The changes in D-Ser levels varied in the 6 patients, with circulating D-Ser levels increasing as much as 35% in a patient, while decreasing 20% in a patient. While only preliminary data, the results suggests the potential importance in determining the D-Ser levels in plasma and their potential role in physiological response.