Determination and pharmacokinetic study of norcantharidin in human serum by HPLC-MS/MS method.
A sensitive, simple and selective high-performance liquid chromatography-tandem mass spectrometry method was developed and applied to the determination of norcantharidin concentration in human serum. Norcantharidin (NCTD) and cyclophosphamide (IS) in serum were extracted with acetone, separated on a C18 reversed-phase column, gradiently eluted with a mobile phase of acetonitrile-water containing 2 mm ammonium acetate and 0.1% formic acid (pH 3), ionized by positive ion pneumatically assisted electrospray and detected in the multi-reaction monitoring mode using precursor-->product ions of m/z 169.3-->123.1 for NCTD and 261.2-->140.2 for IS, respectively. The linear range of the calibration curve for NCTD was 2.5-50 ng/mL, with a lowest limit of quantification of 2.5 ng/mL, and the intra/inter-day RSD was less than 10%. The method was suitable for determination of low NCTD concentration in human serum after therapeutic oral doses, and has been successfully used for pharmacokinetic studies in healthy Chinese volunteers.
Wei
Chun-min
CM
Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan 250012, People's Republic of China.
Zhang
Rui
R
Wang
Ben-jie
BJ
Yuan
Gui-yan
GY
Guo
Rui-chen
RC
D000096:Acetone / Q000737:chemistry; D000097:Acetonitriles / Q000737:chemistry; D000284:Administration, Oral; D000328:Adult; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003520:Cyclophosphamide / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014867:Water / Q000737:chemistry
D000097:Acetonitriles; D019086:Bridged Bicyclo Compounds, Heterocyclic; D014867:Water; D000096:Acetone; C069741:norcantharidin; D003520:Cyclophosphamide; C032159:acetonitrile