Simultaneous determination of levophencynonate and its metabolite demethyl levophencynonate in human plasma by liquid chromatography tandem mass spectrometry.
A sensitive and convenient high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to determine levophencynonate and demethyl levophencynonate levels in human plasma simultaneously. Chromatographic separation was achieved on a SHIMADZU Shim-Pack XR C8 column and mass spectrometric analysis was performed by an API5000 mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transitions of m/z 358.4→156.4 and 344.5→144.2 were used to quantify levophencynonate and demethyl levophencynonate, respectively. This analytical method was fully validated with specificity, linearity, lower limit of quantitation (LLOQ), accuracy, precision, stability, matrix effect and recovery. The linearity of this method were developed to be within the concentration ranges of 10-4000pg/mL for levophencynonate and 25-8000pg/mL for demethyl levophencynonate in human plasma. This method was used in a clinical study which was administrated with single oral dose for Chinese healthy subjects to investigate the pharmacokinetics of levophencynonate and demethyl levophencynonate.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016 Liaoning, China; Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Clinical Pharmacology, Beijing Hospital 100730, China.
Bo
B
Li
Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Clinical Pharmacology, Beijing Hospital 100730, China.
Wenyuan
W
Qi
Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Clinical Pharmacology, Beijing Hospital 100730, China. Electronic address: aixins0302@126.com.
Aixin
A
Shi
Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Clinical Pharmacology, Beijing Hospital 100730, China.
Xin
X
Hu
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016 Liaoning, China. Electronic address: chenggang63@hotmail.com.
Gang
G
Cheng
D001372:Aza Compounds / Q000097:blood* / Q000378:metabolism; D018680:Cholinergic Antagonists / Q000097:blood* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006016:Glycolates / Q000097:blood* / Q000378:metabolism; D006801:Humans; D057230:Limit of Detection; D059625:Liquid-Liquid Extraction / Q000379:methods; D008745:Methylation; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
C504860:3-methyl-3-azabicyclo(3,3,1)nonanyl-9-alpha-yl-alpha-cyclopentyl-alpha-phenyl-alpha-glycolate; D001372:Aza Compounds; D018680:Cholinergic Antagonists; D006016:Glycolates
Demethyl levophencynonate; HPLC–MS/MS; Human plasma; Levophencynonate