固相萃取结合HPLC-MS测定人血浆中奥曲肽的浓度及相对生物利用度固相萃取结合HPLC-MS测定人血浆中奥曲肽的浓度及相对生物利用度

目的建立人血浆中奥曲肽浓度的HPLC-MS测定法，研究国产奥曲肽注射剂的人体生物利用度。方法 血浆样品用HPL 1cc固相萃取小柱萃取，经Waters Xetrra C₁₈ MS分离后测定。18名健康志愿受试者采用随机交叉试验设计，分别im奥曲肽试验制剂和参比制剂200 μg，不同时间点采血，比较两者的生物利用度。结果线性范围0.5～40 μg·L^-1，方法回收率为97.1%～100.5%。日内、日间RSD分别为1.1%～1.6%，2.9%～4.8%。单剂量im奥曲肽200 μg后两种制剂的C_max分别为（19±10） μg·L^-1和（19±11） μg·L^-1，t_max分别为（0.50±0.15） h和（0.52±0.20） h；AUC_0～7h分别为（50±25） h·μg·L^-1和（50±25） h·μg·L^-1，t_1/2分别为(1.5±0.8) h 和(1.5±0.8) h。二者之间均无显著性差异，以进口奥曲肽为参比制剂，国产奥曲肽注射液的相对生物利用度为101%±10%。结论该方法灵敏、准确度高，可用于奥曲肽体内过程研究。两注射剂为生物等效性制剂。

Determination of octreotide in human plasma by HPLC-MS with solid-phase extraction and study on the relative bioavailability of domestic and imported octreotide injections

AIM: To establish an HPLC-MS method for determination of octreotide in plasma and study the relative bioavailability of domestic and imported octreotide injections. METHODS: Octreotide in plasma samples were extracted with a Waters solid-phase extraction mini column. HPLC-MS was carried out using a Waters Xetrra C18 column and a mobile phase consisting of CH3 OH-1% HAc (80 : 20), the flow rate was 0.2 mL x min(-1), and the internal standard was 6, 7, 4'-OH-isoflavone, the SIR ions for quantification were m/z 1 014.4 for octreotide and m/z 317.6 for internal standard. A single dose of 200 microg of domestic or imported preparations was intramuscularly given to 18 healthy volunteers in a randomized crossover study. Octreotide concentration in plasma was determined by LC-MS method. The pharmacokinetics and bioavailability were studied. RESULTS: The regressive curve was linear (r = 0.9997) within the range of 0.5 - 40 microg x L(-1) for octreotide. The pharmacokinetics parameters of domestic and imported injection were reply to one compartment model. The mean C(max) were (19 +/- 10) microg x L(-1) and (19 +/- 11) microg x L(-1), T(max) were (0.50 +/- 0.15) h and (0.52 +/- 0.20) h, T1/2 were (1.5 +/- 0.8) h and (1.5 +/- 0.8) h, AUC(0-7 h) were (50 +/- 25) h x microg x L(-1) and (50 +/- 25) h x microg x L(-1), respectively. The relative bioavailability of domestic to imported injection was 101% +/- 10%. CONCLUSION: The method is accurat and sensible for assay of plasma octreotide concentration. The results of statistics showed the two preparations were bioequivalent.