title: Validation of a sensitive LC/MS/MS method for simultaneous quantitation of flupentixol and melitracene in human plasma.
abstract: A sensitive method has been developed and validated, using LC/ESI-MS/MS, for simultaneous quantitation of flupentixol and melitracen--antidepressant drugs, in human plasma. The quantitation of the target compounds was determined in a positive ion mode and multiple reaction monitoring (MRM). The method involved a repeated liquid-liquid extraction with diethyl ether and analytes were chromatographed on a C(8) chromatographic column by elution with acetonitrile-water-formic acid (36:64:1, v/v/v) and analyzed by tandem mass spectrometry. The method was validated over the concentration ranges of 26.1-2090 pg/ml for flupentixol and 0.206-4120 ng/ml for melitracen. The correlation coefficients of both analyst were >0.998 for six sets of calibration curves. The recovery was 60.9-75.1% for flupentixol, melitracen and internal standard. The lower limit of quantitation (LLOQ) detection was 26.1 pg/ml for flupentixol and 0.206 ng/ml for melitracen. Intra- and inter-day precision of the assay at three concentrations were 2.15-5.92% with accuracy of 97.6-103.0% for flupentixol and 0.5-6.36% with accuracy of 98.7-101.7% for melitracen. Stability of compounds was established in a battery of stability studies, i.e., bench-top, autosampler and long-term storage stability as well as freeze/thaw cycles. The method proved to be suitable for bioequivalence study of flupentixol and melitracen in healthy human male volunteers.
authors: Lab of Drug Metabolism and Pharmacokinetics, The Institute of Microbiology & Epidemiology, The Academy of Military Medical Sciences, No. 20, Dongda Street, Fengtai District, Beijing, PR China.
authors: Jinjing
authors: J
authors: Che
authors: Qingfang
authors: Q
authors: Meng
authors: Zhihang
authors: Z
authors: Chen
authors: Chengqi
authors: C
authors: San
authors: Yunan
authors: Y
authors: Hou
authors: Yuanguo
authors: Y
authors: Cheng
mesh_terms: D000873:Anthracenes / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D014150:Antipsychotic Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D005475:Flupenthixol / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D005615:Freezing; D006801:Humans; D008297:Male; D015394:Molecular Structure; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013696:Temperature; D013810:Therapeutic Equivalency
chemical_list: D000873:Anthracenes; D014150:Antipsychotic Agents; C005100:melitracene; D005475:Flupenthixol