HPLC-MS测定血浆中的奥曲肽药物浓度

Determination of octreotide in the human plasma by HPLC-MS

目的 建立血浆中奥曲肽药物浓度的测定方法并应用于药物动力学研究。方法采用Waters Micromass ZQ液相色谱-质谱联用仪。色谱条件：WatersC18（150mm×3．9mm，2．1μm）色谱柱；流动相为乙腈-水-甲酸（20：80：0．1），流速为0．2mL·min^-1；质谱条件：Micromass ZQ电喷雾质谱仪，离子源：ESI；极性（检出模式）。结果奥曲肽在选择离子通道上的保留时间为7．38min，内标在选择通道（m／z）保留时间为8．65min，奥曲肽的血药浓度范围为0．50-40．00ng·mL^-1，定量下限为0．50ng·mL^-1，日内、日间误差〈12％。用此方法测定了18例志愿者皮下注射0．1mg的醋酸奥曲肽后的血药浓度。结论该方法简单、灵敏、可靠，适合体内奥曲肽的药物动力学研究。

OBJECTIVE A selective and sensitive liquid chromatographic-mass spectrometric method was developed to determine octreotide in the plasma, and to study its pharmacokinetics. METHODS Blood samples were injected after solid-phase extraction extraction. The chromatographic separation was achieved on a C18 reversed-phase column using acetonitrile-water-formic acid （20 ： 80 ： 0.1, V/V/V） as the mobile phase. The mass spectrometric analysis was performed by electro-spray in positive ion mode. Selective （single） ion scan mode of m/z 1 019.0 and 765.0 were used to quantitatively determine octreotide and the l. S. , respectively. RESULTS The assay exhibited a linear range of 0. 50-40.00 ng · mL^-1. The low limit of the quantitation was 0.50 ng · mL^-1. Recovery was 97.0%- 100.8 %. The precision of the method were 4.4 % - 11.5 %. After subcutaneous administration of 0. 1 mg acetate octreotide injection to 18 healthy subjects, the pharmacokinetic parameters： AUC0-t, （41. 13 ± 13.50） ng · h · mL^-1, Cmax （18.44±4.58） ng· mL^-1, tmax （0.53±0.15） h, t1/2 （1.81±0.36） h, K0 （0.39±0.07） h ^-1. CONCLUSIONS The method is sensitive, accurate, special＇ and reliable. It is suitable to study pharmacokinetics of octreotide.