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Simultaneous determination of morphine-6-d-glucuronide, morphine-3-d-glucuronide and morphine in human plasma and urine by ultra-performance liquid chromatography-tandem mass spectrometry: Application to M6G injection pharmacokinetic study.
Biomed Chromatogr. 2018 Feb; 32(2)BC

Abstract

A robust ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of morphine-6-d-glucuronide (M6G), morphine-3-d-glucuronide (M3G) and morphine (MOR) in human plasma and urine has been developed and validated. The analytes of interest were extracted from plasma by protein precipitation. The urine sample was prepared by dilution. Both plasma and urine samples were chromatographed on an Acquity UPLC HSS T3 column using gradient elution. Detection was performed on a Xevo TQ-S tandem mass spectrometer in multiple reaction monitoring mode using positive electrospray ionization. Matrix interferences were not observed at the retention time of the analytes and internal standard, naloxone-D5. The lower limits of quantitation of plasma and urine were 2/0.5/0.5 and 20/4/2 ng/mL for M6G/M3G/MOR, respectively. Calibration curves were linear over the concentration ranges of 2-2000/0.5-500/0.5-500 and 20-20,000/4-4000/2-2000 ng/mL for M6G/M3G/MOR in plasma and urine samples, respectively. The precision was <7.14% and the accuracy was within 85-115%. Furthermore, stability of the analytes at various conditions, dilution integrity, extraction recovery and matrix effect were assessed. Finally, this quantitative method was successfully applied to the pharmacokinetic study of M6G injection in Chinese noncancer pain patients.

Authors+Show Affiliations

Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28833311

Citation

Xu, Wen, et al. "Simultaneous Determination of Morphine-6-d-glucuronide, Morphine-3-d-glucuronide and Morphine in Human Plasma and Urine By Ultra-performance Liquid Chromatography-tandem Mass Spectrometry: Application to M6G Injection Pharmacokinetic Study." Biomedical Chromatography : BMC, vol. 32, no. 2, 2018.
Xu W, Zhuang Q, Chen X, et al. Simultaneous determination of morphine-6-d-glucuronide, morphine-3-d-glucuronide and morphine in human plasma and urine by ultra-performance liquid chromatography-tandem mass spectrometry: Application to M6G injection pharmacokinetic study. Biomed Chromatogr. 2018;32(2).
Xu, W., Zhuang, Q., Chen, X., Jiang, J., Hu, P., & Wang, H. (2018). Simultaneous determination of morphine-6-d-glucuronide, morphine-3-d-glucuronide and morphine in human plasma and urine by ultra-performance liquid chromatography-tandem mass spectrometry: Application to M6G injection pharmacokinetic study. Biomedical Chromatography : BMC, 32(2). https://doi.org/10.1002/bmc.4066
Xu W, et al. Simultaneous Determination of Morphine-6-d-glucuronide, Morphine-3-d-glucuronide and Morphine in Human Plasma and Urine By Ultra-performance Liquid Chromatography-tandem Mass Spectrometry: Application to M6G Injection Pharmacokinetic Study. Biomed Chromatogr. 2018;32(2) PubMed PMID: 28833311.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simultaneous determination of morphine-6-d-glucuronide, morphine-3-d-glucuronide and morphine in human plasma and urine by ultra-performance liquid chromatography-tandem mass spectrometry: Application to M6G injection pharmacokinetic study. AU - Xu,Wen, AU - Zhuang,Quankun, AU - Chen,Xia, AU - Jiang,Ji, AU - Hu,Pei, AU - Wang,Hongyun, Y1 - 2017/09/15/ PY - 2017/05/19/received PY - 2017/07/25/revised PY - 2017/08/14/accepted PY - 2017/8/24/pubmed PY - 2018/2/24/medline PY - 2017/8/24/entrez KW - UPLC-MS/MS KW - morphine KW - morphine-3-d-glucuronide KW - morphine-6-d-glucuronide JF - Biomedical chromatography : BMC JO - Biomed Chromatogr VL - 32 IS - 2 N2 - A robust ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of morphine-6-d-glucuronide (M6G), morphine-3-d-glucuronide (M3G) and morphine (MOR) in human plasma and urine has been developed and validated. The analytes of interest were extracted from plasma by protein precipitation. The urine sample was prepared by dilution. Both plasma and urine samples were chromatographed on an Acquity UPLC HSS T3 column using gradient elution. Detection was performed on a Xevo TQ-S tandem mass spectrometer in multiple reaction monitoring mode using positive electrospray ionization. Matrix interferences were not observed at the retention time of the analytes and internal standard, naloxone-D5. The lower limits of quantitation of plasma and urine were 2/0.5/0.5 and 20/4/2 ng/mL for M6G/M3G/MOR, respectively. Calibration curves were linear over the concentration ranges of 2-2000/0.5-500/0.5-500 and 20-20,000/4-4000/2-2000 ng/mL for M6G/M3G/MOR in plasma and urine samples, respectively. The precision was <7.14% and the accuracy was within 85-115%. Furthermore, stability of the analytes at various conditions, dilution integrity, extraction recovery and matrix effect were assessed. Finally, this quantitative method was successfully applied to the pharmacokinetic study of M6G injection in Chinese noncancer pain patients. SN - 1099-0801 UR - https://www.unboundmedicine.com/medline/citation/28833311/Simultaneous_determination_of_morphine_6_d_glucuronide_morphine_3_d_glucuronide_and_morphine_in_human_plasma_and_urine_by_ultra_performance_liquid_chromatography_tandem_mass_spectrometry:_Application_to_M6G_injection_pharmacokinetic_study_ L2 - https://doi.org/10.1002/bmc.4066 DB - PRIME DP - Unbound Medicine ER -