Laboratory of Clinical Investigation, Division of Intramural Research Programs, National institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Aug 15;933:37-43. doi: 10.1016/j.jchromb.2013.06.020. Epub 2013 Jun 26.
Due to the lack of sensitivity in current methods for the determination of fenoterol (Fen), a rapid LC-MS/MS method was developed for the determination of (R,R')-Fen and (R,R';S,S')-Fen in plasma and urine. The method was fully validated and was linear from 50pg/ml to 2000pg/ml for plasma and from 2.500ng/ml to 160ng/ml for urine with a lower limit of quantitation of 52.8pg/ml in plasma. The coefficient of variation was <15% for the high QC standards and <10% for the low QC standards in plasma and was <15% for the high and low QC standards in urine. The relative concentrations of (R,R')-Fen and (S,S')-Fen were determined using a chirobiotic T chiral stationary phase. The method was used to determine the concentration of (R,R')-Fen in plasma and urine samples obtained in an oral cross-over study of (R,R')-Fen and (R,R';S,S')-Fen formulations. The results demonstrated a potential pre-systemic enantioselective interaction in which the (S,S')-Fen reduces the sulfation of the active (R,R')-Fen. The data suggest that a non-racemic mixture of the Fen enantiomers may provide better bioavailability of the active (R,R')-Fen for use in the treatment of cardiovascular disease.
由于目前测定芬特罗（Fen）的方法灵敏度不足，因此开发了一种快速 LC-MS/MS 方法，用于测定血浆和尿液中的（R,R'）-芬特罗和（R,R';S,S'）-芬特罗。该方法经过全面验证，在血浆中线性范围为 50pg/ml 至 2000pg/ml，在尿液中线性范围为 2.500ng/ml 至 160ng/ml，定量下限为 52.8pg/ml。高、低 QC 血浆标准品的变异系数均<15%，高、低 QC 尿液标准品的变异系数均<15%。（R,R'）-芬特罗和（S,S'）-芬特罗的相对浓度使用手性固定相 chirobiotic T 来确定。该方法用于测定口服交叉研究中（R,R'）-芬特罗和（R,R';S,S'）-芬特罗制剂获得的血浆和尿液样品中（R,R'）-芬特罗的浓度。结果表明存在潜在的预系统性对映选择性相互作用，其中（S,S'）-芬特罗降低了活性（R,R'）-芬特罗的硫酸化。数据表明，芬特罗对映异构体的非外消旋混合物可能为治疗心血管疾病提供更好的活性（R,R'）-芬特罗的生物利用度。
