Wang Rulin, Zhang Lin, Zhang Zunjian, Tian Yuan
Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China.
State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China.
J Pharm Anal. 2016 Dec;6(6):356-362. doi: 10.1016/j.jpha.2016.03.006. Epub 2016 Mar 29.
Electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) techniques for liquid chromatography-tandem mass spectrometry (LC-MS/MS) determination of levonorgestrel were evaluated. In consideration of difference in ionization mechanism, the two ionization sources were compared in terms of LC conditions, MS parameters and performance of method. The sensitivity for detection of levonorgestrel with ESI was 0.25 ng/mL which was lower than 1 ng/mL with APCI. Matrix effects were evaluated for levonorgestrel and canrenone (internal standard, IS) in human plasma, and the results showed that APCI source appeared to be slightly less liable to matrix effect than ESI source. With an overall consideration, ESI was chosen as a better ionization technique for rapid and sensitive quantification of levonorgestrel. The optimized LC-ESI-MS/MS method was validated for a linear range of 0.25-50 ng/mL with a correlation coefficient ≥0.99. The intra- and inter-batch precision and accuracy were within 11.72% and 6.58%, respectively. The application of this method was demonstrated by a bioequivalence study following a single oral administration of 1.5 mg levonorgestrel tablets in 21 Chinese healthy female volunteers.
对用于液相色谱-串联质谱法（LC-MS/MS）测定左炔诺孕酮的电喷雾电离（ESI）和大气压化学电离（APCI）技术进行了评估。考虑到电离机制的差异，从液相色谱条件、质谱参数和方法性能等方面对这两种电离源进行了比较。用ESI检测左炔诺孕酮的灵敏度为0.25 ng/mL，低于用APCI时的1 ng/mL。对人血浆中的左炔诺孕酮和坎利酮（内标，IS）进行了基质效应评估，结果表明APCI源似乎比ESI源对基质效应的敏感性略低。综合考虑，ESI被选为用于快速灵敏定量左炔诺孕酮的更佳电离技术。优化后的LC-ESI-MS/MS方法在0.25 - 50 ng/mL的线性范围内得到验证，相关系数≥0.99。批内和批间精密度及准确度分别在11.72%和6.58%以内。在21名中国健康女性志愿者单次口服1.5 mg左炔诺孕酮片后进行的生物等效性研究证明了该方法的应用。
