Lukram Ojit Kumar, Sharma Ramkishor
LifeSan Clinical Research, Division of Centaur Pharmaceuticals Pvt. Ltd, Centaur House, Near Hotel Grand Hyatt, Vakola, Santacruz (E), Mumbai, 400055, India.
Biomed Chromatogr. 2014 Aug;28(8):1147-55. doi: 10.1002/bmc.3136. Epub 2014 Feb 24.
A simple and sensitive liquid chromatography tandem mass spectrometry method has been developed for the quantification of ambrisentan (AMB) in human plasma using midazolam (MID) as an internal standard (IS). Chromatographic separation was performed using a Beta Basic-8 (50 × 4.6 mm, 5 µm) column with an isocratic mobile phase. AMB and MID were detected with proton adducts at m/z 379.09 → 303.12 and 326.15 → 291.14 in multiple reaction monitoring-positive mode, respectively. A solid-phase extraction method was used for extraction of the analyte and IS from the plasma samples. The method was shown to be reproducible and reliable with within-run precision <11%, between-run precision <14% and linear concentration range from 10.0 to 2000.2 ng/mL, with a correlation coefficient (r(2) ) of >0.995. The method was successfully applied to a pharmacokinetic study of oral administration of AMB (10 mg) in 24 healthy Indian male human volunteers under fasting conditions.
已开发出一种简单且灵敏的液相色谱串联质谱法，以咪达唑仑（MID）作为内标（IS），用于定量测定人血浆中的安立生坦（AMB）。使用Beta Basic - 8（50×4.6 mm，5 µm）色谱柱和等度流动相进行色谱分离。在多反应监测阳性模式下，分别在m/z 379.09→303.12和326.15→291.14处检测到AMB和MID的质子加合物。采用固相萃取法从血浆样品中提取分析物和内标。该方法具有重现性和可靠性，批内精密度<11%，批间精密度<14%，线性浓度范围为10.0至2000.2 ng/mL，相关系数（r(2)）>0.995。该方法已成功应用于24名健康印度男性人类志愿者在禁食条件下口服AMB（10 mg）的药代动力学研究。
