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目的:建立大鼠血浆中盐酸噻吩诺啡的液质联用测定法(LC-MS/MS法),比较盐酸噻吩诺啡片剂和鼻腔喷雾剂的生物利用度。方法:血浆中加入内标丁丙诺啡后甲醇沉淀蛋白。流动相:乙腈-0.01%甲酸,梯度洗脱,流速为0.5 mL.min-1,柱后分流。色谱柱:Agilent-C18柱(150 mm×2.1 mm,5 mm)。离子化方式:电喷雾离子化。多反应监测(multiple reaction monitoring,MRM):定量离子对,噻吩诺啡m/z522.5→m/z97.1,内标丁丙诺啡为m/z468.5→m/z396.2。结果:盐酸噻吩诺啡鼻腔喷雾剂、片剂的绝对生物利用度分别(70.84±51.16)%和(1.22±0.16)%,鼻喷剂的生物利用度极明显高于片剂(>58倍),其血药峰浓度明显大于口服给药。结论:建立了简单快速、特异性强且灵敏度高的LC-MS/MS法,用于盐酸噻吩诺啡的体内定量分析。盐酸噻吩诺啡鼻喷剂显著提高了其在大鼠体内的生物利用度,为临床应用提供一种新的剂型选择。
Objective: To establish a liquid chromatography-mass spectrometry (LC-MS / MS) method for the determination of thienorphine hydrochloride in rat plasma and to compare the bioavailability of thienorphine hydrochloride tablets and nasal spray. METHODS: Methanol precipitated protein was added to the plasma after the addition of internal standard buprenorphine. Mobile phase: acetonitrile -0.01% formic acid, gradient elution, flow rate of 0.5 mL.min-1, post-column shunt. Column: Agilent-C18 column (150 mm × 2.1 mm, 5 mm). Ionization: Electrospray ionization. Multiple reaction monitoring (MRM): quantitative ion pair, thienorphine m / z 522.5 → m / z 97.1, and internal standard buprenorphine m / z 468.5 → m / z 396.2. Results: The absolute bioavailability of thienorphine hydrochloride nasal spray and tablet were (70.84 ± 51.16)% and (1.22 ± 0.16)%, respectively. The bioavailability of nasal spray was significantly higher than that of tablet (> 58 times) , The peak plasma concentration was significantly greater than oral administration. Conclusion: The LC-MS / MS method is simple, rapid, specific and sensitive for the quantitative analysis of thienorphine hydrochloride in vivo. Thienorphine hydrochloride nasal spray significantly increased its bioavailability in rats and provided a new dosage form for clinical application.