Validation of LC-MS electrospray ionisation method for quantitation of haloperidol in human plasma and its application to bioequivalence study
Validation of LC-MS electrospray ionisation method for quantitation of haloperidol in human plasma and its application to bioequivalence study
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LC-MS 电喷雾电离法定量人血浆中氟哌啶醇的验证及其在生物等效性研究中的应用
DOI：
10.1016/j.aca.2005.07.046
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发表时间：
2005
影响因子：
6.2
通讯作者：
Kuldeep Sharma
中科院分区：
文献类型：
--
作者：
S. S. Singh;Kuldeep Sharma
建立了一种新的灵敏的LC/MS电喷雾电离质谱法测定人血浆中抗精神病药物氟哌啶醇的浓度。该方法是为了准确测定参加印度卡迪拉健康护理有限公司M/S 5 mg氟哌啶醇片生物等效性研究的受试者的血药浓度，与美国日内瓦制药公司的5 mg氟哌啶醇片进行生物等效性研究。以度洛西汀为内标，采用液-液萃取(LLE)法进行样品净化和预浓缩。色谱柱为Xterra MS C18 100 mm×2.1 mm，3.5min，流速为0.2ml/μ。在阳性模式下进行质谱学检测，定量下限(LLOQ)为70.0pg/ml。测定了氟哌啶醇和内标的离子信号m/z分别为375.9和297.9。根据美国食品和药物管理局的指南进行了详尽的研究前方法验证。标准曲线在70.0pg/ml~14.0 ng/ml范围内线性关系良好，平均相关系数为0.998。该方法已成功地用于氟哌啶醇在健康男性志愿者体内的生物等效性研究。
In the present investigation, a new sensitive LC/MS electrospray ionisation mass spectrometric method has been developed for the quantitation of haloperidol—an antipsychotic drug, in human plasma. The method was developed with the objective of accurately measuring the concentration of haloperidol in the plasma of human subjects enrolled in the bioequivalence study of haloperidol (5mg) tablets of M/s. Cadila Health Care Ltd. India versus 5mg haloperidol tablets of Geneva Pharma USA. The sample purification and pre-concentration was performed by liquid–liquid extraction (LLE) using duloxetine as internal standard. The chromatographic separation was achieved using an isocratic mobile phase containing 1.0mM ammonium acetate pH 3.0 and acetonitrile (70:30, v/v) flowing through Xterra MS C18 100mm×2.1mm, 3.5μm analytical column, at a flow rate of 0.2ml/min. The lower limit of quantitation (LLOQ) of 70.0pg/ml was achieved using mass spectrometric detection in positive mode. The ion signals of m/z 375.9 and 297.9 were measured for haloperidol and internal standard, respectively. An exhaustive pre-study method validation was performed in accordance with USFDA guidelines. The standard curves were linear in the concentration range of 70.0pg/ml to 14.0ng/ml with mean correlation coefficient of 0.998. The method was successfully applied to the bioequivalence study of haloperidol in healthy human male volunteers.