Development and validation of a sensitive LC–MS/MS method for the determination of d-serine in human plasma

Abstract 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 six 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.