Zhang Guodong, Terry Alvin V, Bartlett Michael G
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602-2352, USA.
Biomed Chromatogr. 2008 Jul;22(7):770-8. doi: 10.1002/bmc.999.
A simple, sensitive and robust liquid chromatography/electrospray ionization tandem mass spectrometry (LCESI-MS/MS) method with low matrix effects was developed and validated for the quantification of the lipophilic antipsychotic ziprasidone from rat plasma and brain tissue. Ziprasidone was extracted from rat plasma and brain homogenate using a single-step liquid-liquid extraction. Ziprasidone was separated on an Agilent Eclipse XDB C8 column (150 x 2.1 mm i.d., 5 microm) column using a mobile phase of acetonitrile-0.02% ammonia in water (pH 7.20 adjusted with formic acid) using gradient elution. Ziprasidone was detected in the positive ion mode using multiple reaction monitoring. The method was validated and the specificity, linearity, lower limit of quantitation (LLOQ), precision, accuracy, recovery, matrix effects and stability were determined. The LLOQ was 0.2 ng/mL for plasma and 0.833 ng/g for brain tissue. The method was linear over the concentration range from 0.2 to 200.0 ng/mL for plasma and 0.833-833.3 ng/g for brain tissue. The correlation coefficient (R2) values were more than 0.996 for both plasma and brain homogenate. The precision and accuracy intra-day and inter-day were better than 8.13%. The relative and absolute recovery was above 81.0% and matrix effects were lower than 5.2%. This validated method has been successfully used to quantify the rat plasma and brain tissue concentration of ziprasidone after chronic treatment.
建立了一种简单、灵敏且稳健的液相色谱/电喷雾电离串联质谱法（LC-ESI-MS/MS），该方法具有较低的基质效应，用于定量大鼠血浆和脑组织中的亲脂性抗精神病药物齐拉西酮。采用单步液液萃取法从大鼠血浆和脑匀浆中提取齐拉西酮。使用乙腈-0.02%氨水溶液（用甲酸调节pH至7.20）作为流动相，采用梯度洗脱，在安捷伦Eclipse XDB C8柱（150×2.1 mm内径，5μm）上分离齐拉西酮。采用多反应监测在正离子模式下检测齐拉西酮。对该方法进行了验证，并测定了特异性、线性、定量下限（LLOQ）、精密度、准确度、回收率、基质效应和稳定性。血浆的LLOQ为0.2 ng/mL，脑组织的LLOQ为0.833 ng/g。该方法在血浆浓度范围为0.2至200.0 ng/mL、脑组织浓度范围为0.833至833.3 ng/g时呈线性。血浆和脑匀浆的相关系数（R2）值均大于0.996。日内和日间精密度和准确度均优于8.13%。相对回收率和绝对回收率均高于81.0%，基质效应低于5.2%。该经过验证的方法已成功用于定量慢性治疗后大鼠血浆和脑组织中齐拉西酮的浓度。
