Avula Bharathi, Khan Shabana I, Tekwani Babu L, Nanayakkara N P Dhammika, McChesney James D, Walker Larry A, Khan Ikhlas A
National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, MS 38677, USA.
Biomed Chromatogr. 2011 Sep;25(9):1010-7. doi: 10.1002/bmc.1557. Epub 2010 Nov 5.
The clinical formulation of primaquine (PQ) is a mixture of (-)-(R)- and (+)-(S)- primaquine enantiomers which may show different pharmacokinetic and pharmacodynamic properties. To assess the efficacy and toxicity of primaquine enantiomers, a method using LC-MSD-TOF has been developed. The enantiomers were well separated using a Chiralcel OD column (250 × 4.6 mm, 10 µm) with a linear gradient of mobile phase consisting of acetonitrile (0.1% formic acid) and aqueous ammonium formate (20 mm; 0.1% formic acid) adjusted to pH 5.9 at a flow rate of 0.7 mL/min. The method was validated for linearity, precision, accuracy and limits of detection and quantification. The calibration curves were linear with all correlation coefficients being >0.999. The average recoveries of (-)-(R)- and (+)-(S)-primaquine and (-)-(R)- and (+)-(S)-carboxyprimaquine were 88 and 92%, respectively, in spiked human plasma and 89 and 93% respectively in spiked mouse plasma samples. The RSD of (-)-(R)- and (+)-(S)-primaquine and (-)-(R)- and (+)-(S)-carboxyprimaquine were 2.15, 1.74, 1.73 and 2.31, respectively, in spiked human plasma and 2.21, 1.09, 1.95 and 1.17% in spiked mouse plasma, respectively. The intra-day and inter-day precisions expressed as RSD were lower than 10% in all analyzed quality control levels. The method as reported is suitable for study of the pharmacokinetic and pharmacodynamic properties of the enantiomers of primaquine. The method was successfully applied to study plasma pharmacokinetic profile of enantiomers of primaquine and carboxyprimaquine in mice administered with primaquine in racemic form. The analytical method was found to be linear, accurate, precise and specific.
伯氨喹（PQ）的临床制剂是（-）-（R）-和（+）-（S）-伯氨喹对映体的混合物，它们可能表现出不同的药代动力学和药效学特性。为了评估伯氨喹对映体的疗效和毒性，已开发出一种使用液相色谱-质谱-飞行时间（LC-MSD-TOF）的方法。使用Chiralcel OD柱（250×4.6 mm，10 µm），以乙腈（0.1%甲酸）和甲酸铵水溶液（20 mM；0.1%甲酸）组成的流动相线性梯度，将pH调节至5.9，流速为0.7 mL/min，可很好地分离对映体。该方法在线性、精密度、准确度以及检测和定量限方面得到了验证。校准曲线呈线性，所有相关系数均>0.999。在加标的人血浆中，（-）-（R）-和（+）-（S）-伯氨喹以及（-）-（R）-和（+）-（S）-羧基伯氨喹的平均回收率分别为88%和92%，在加标的小鼠血浆样品中分别为89%和93%。在加标的人血浆中，（-）-（R）-和（+）-（S）-伯氨喹以及（-）-（R）-和（+）-（S）-羧基伯氨喹的相对标准偏差（RSD）分别为2.15%、1.74%、1.73%和2.31%，在加标的小鼠血浆中分别为2.21%、1.09%、1.95%和1.17%。在所有分析的质量控制水平下，以RSD表示的日内和日间精密度均低于10%。所报道的该方法适用于研究伯氨喹对映体的药代动力学和药效学特性。该方法已成功应用于研究以消旋形式给予伯氨喹的小鼠体内伯氨喹和羧基伯氨喹对映体的血浆药代动力学概况。发现该分析方法具有线性、准确、精密和特异的特点。
