Determination of naloxone-3-glucuronide in human plasma and urine by HILIC-MS/MS.
A hydrophilic interaction chromatography-tandem mass spectrometric (HILIC-MS/MS) method was developed for the direct determination of naloxone-3-glucuronide (N3G) in human plasma and urine. After a straightforward sample preparation by protein precipitation, N3G was analyzed directly without the need for hydrolysis. Chromatographic separation was performed on a HILIC column. The mobile phase was composed of acetonitrile-10mmol/L ammonium formate (86:14, v/v), with a flow rate of 0.4mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via positive electrospray ionisation (ESI+) source. The linear calibration range was 0.5 to 200ng/mL in plasma and 10 to 5000ng/mL in urine (r(2)>0.99). The intra- and inter-day precision (relative standard deviation, RSD) values were below 15% and the accuracies (relative error, RE) were -7.1% to 2.8% in plasma and -1.3% to 10.3% in urine at three quality control levels. In human subjects receiving 100mg tilidine and 8mg naloxone, mean AUC0-24 of N3G was 160.93±52.77ng/mLh and mean Cmax was 75.33±25.27ng/mL. In 24-h urine samples, 8.0% of the dose was excreted in the form of N3G in urine. These results demonstrated a new method suitable for in vivo pharmacokinetic studies of N3G.
Department of Clinical Pharmacology Research Lab, The First Affiliated Hospital of Soochow University, no. 188 Shi zi Street, Suzhou 215006, China; Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, China.
Ji
J
Dong
Shuaibing
S
Liu
Hua
H
Zhang
Qianli
Q
Hua
Xuegang
X
Zhao
Liyan
L
Miao
D000284:Administration, Oral; D000328:Adult; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D057230:Limit of Detection; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
D009270:Naloxone; C518509:naloxone-3-glucuronide
HILIC–MS/MS; Naloxone-3-glucuronide; Pharmacokinetics