Wu Y, Zhao J, Henion J, Korfmacher W A, Lapiguera A P, Lin C C
Advanced BioAnalytical Services, Inc., Ithaca, New York 14850, USA.
J Mass Spectrom. 1997 Apr;32(4):379-87. doi: 10.1002/(SICI)1096-9888(199704)32:4<379::AID-JMS461>3.0.CO;2-9.
A sensitive and specific method was developed and validated to quantitate lovastatin and its hydroxy acid in mouse and rat plasma. This method employs a solid-phase extraction procedure to isolate lovastatin and its hydroxy acid metabolite from the biological matrices (0.1 ml of mouse or rat plasma). The reconstituted extracts were analyzed by liquid chromatography/ionspray tandem mass spectrometry (LC/MS/MS). Simvastatin and simvastatin hydroxy acid were used as internal standards for lovastatin and lovastatin hydroxy acid, respectively. The assay has a lower limit of quantitation (LLQ) of 0.50 ng ml-1 in mouse and rat plasma for both lovastatin and its hydroxy acid based on 0.1 ml aliquots of plasma. The intra- and inter-assay precision (RSD), calculated from quality control (QC) samples, was < 7% for lovastatin and < 6% for lovastatin hydroxy acid in both matrices. The inter-assay accuracy as determined from QC samples was less than 6% for lovastatin and less than 8% for lovastatin hydroxy acid in both matrices. The overall recovery of lovastatin was 54% in mouse plasma and 55% in rat plasma, and the overall recovery of lovastatin hydroxy acid was 100% in mouse plasma and 67% in rat plasma.
开发并验证了一种灵敏且特异的方法，用于定量测定小鼠和大鼠血浆中的洛伐他汀及其羟酸。该方法采用固相萃取程序，从生物基质（0.1 ml小鼠或大鼠血浆）中分离洛伐他汀及其羟酸代谢物。用液相色谱/离子喷雾串联质谱法（LC/MS/MS）分析重构提取物。辛伐他汀和辛伐他汀羟酸分别用作洛伐他汀和洛伐他汀羟酸的内标。基于0.1 ml血浆等分试样，该测定法对小鼠和大鼠血浆中洛伐他汀及其羟酸的定量下限（LLQ）均为0.50 ng/ml-1。由质量控制（QC）样品计算得出的批内和批间精密度（RSD），在两种基质中，洛伐他汀均<7%，洛伐他汀羟酸均<6%。由QC样品确定的批间准确度，在两种基质中，洛伐他汀均小于6%，洛伐他汀羟酸均小于8%。洛伐他汀在小鼠血浆中的总回收率为54%，在大鼠血浆中为55%；洛伐他汀羟酸在小鼠血浆中的总回收率为100%，在大鼠血浆中为67%。
