Determination of zolmitriptan in human plasma by liquid chromatography-tandem mass spectrometry method: application to a pharmacokinetic study.
A sensitive and selective liquid chromatography-tandem spectrometry method for the determination of zolmitriptan was developed and validated over the linearity range 0.05-30 ng/ml with 0.5 ml of plasma using diphenhydramine as the internal standard. Liquid-liquid extraction using a mixture of diethyl ether and dichloromethane was used to extract the drug and the internal standard from plasma. The mass spectrometer was operated under the selected reaction monitoring (SRM) mode using the atmospheric pressure chemical ionization (APCI) technique. The instrument parameters were optimized to obtain 3.0 min run time. The mobile phase consisted of acetonitrile-water-formic acid (70:30:0.5), at a flow rate of 0.5 ml/min. In positive mode, zolmitriptan produced a protonated precursor ion at m/z 288 and a corresponding product ion at m/z 58. And internal standard produced a protonated precursor ion at m/z 256 and a corresponding product ion at m/z 167. The inter- and intra-day precision (%R.S.D.) were less than 8.5% and accuracy (%error) was less than -2.5%. The method had a lower limit of quantification of 0.05 ng/ml for zolmitriptan, which offered increased sensitivity and selectivity of analysis, compared with existing methods. The method was successfully applied to a pharmacokinetic study of zolmitriptan after an oral administration of 5 mg zolmitriptan to 20 healthy volunteers.
Chen
Xiaoyan
X
Center for Drug Metabolism and Pharmacokinetics Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 646 Songtao Road, Shanghai 201203, PR China.
Liu
Dan
D
Luan
Yan
Y
Jin
Fengdan
F
Zhong
Dafang
D
D000284:Administration, Oral; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D023303:Oxazolidinones / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D012015:Reference Standards; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D014363:Tryptamines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
D023303:Oxazolidinones; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C089750:zolmitriptan