College of Pharmacy, Chungnam National University, Daejeon 34134, Korea; Life Science Research Institute, Daewoong Pharmaceuticals, Yongin-si 17028, Korea.
Life Science Research Institute, Daewoong Pharmaceuticals, Yongin-si 17028, Korea.
J Chromatogr B Analyt Technol Biomed Life Sci. 2022 Jan 1;1188:123078. doi: 10.1016/j.jchromb.2021.123078. Epub 2021 Dec 4.
Lanreotide is similar to a naturally occurring hormone, somatostatin; thus, it may be used to treat acromegaly or metastatic gastroenteropancreatic neuroendocrine tumours. Here, a bioanalytical method coupling ultra-performance liquid chromatography with tandem mass spectrometry to quantify lanreotide and an internal standard (IS) was developed and validated in dog plasma. The plasma samples were extracted using typical protein precipitation processes. The analyte and internal standard were separated on Phenomenex Kinetex® C18 with 0.1% formic acid and acetonitrile in the mobile phase at a flow rate of 0.4 mL/min. The fragmentation of precursor ions to product ions was optimized at m/z 548.8 → 170.0 for lanreotide [M + 2H] and 472.2 → 436.2 for IS [M + H]. The peak retention times of lanreotide and IS were 1.09 min and 1.22 min, respectively. The calibration curve samples in dog plasma ranged from 0.3 to 1000 ng/mL and showed good linearity, with a correlation coefficient of r=0.9996. The lower limit of quantitation was 0.3 ng/mL. The intra- and inter-day precision (relative standard deviation) values for each quality control level were < 9.7 % and < 9.3 %, respectively; intra- and inter-day accuracy were < 109.3% and < 110.4%, respectively. Lanreotide in dog plasma was stable in various conditions. The maximum plasma concentration of lanreotide in male beagle dogs after subcutaneous injection of Somatuline® (lanreotide) Autogel 120 mg was 88.1 ng/mL. The half-life (T) of lanreotide in beagle dogs was long, approximately 198.6 h; the area under the plasma-concentration curve from 0 to 840 h (day 35) was 6,995 ng⋅h/mL. This novel quantification method using UPLC-MS/MS was successfully applied to the pharmacokinetic analysis of lanreotide in dog plasma. The results will assist future studies of drug formulation and repurposing.
兰瑞肽类似一种天然存在的激素，生长抑素；因此，它可用于治疗肢端肥大症或转移性胃肠胰腺神经内分泌肿瘤。在这里，建立并验证了一种超高效液相色谱-串联质谱法来定量分析狗血浆中的兰瑞肽和内标物（IS）的生物分析方法。该方法采用典型的蛋白沉淀法提取血浆样品。分析物和内标物在 Phenomenex Kinetex® C18 上以 0.1%甲酸和乙腈作为流动相分离，流速为 0.4 mL/min。通过母离子到子离子的碎裂，兰瑞肽[M+2H]的前体离子优化到 m/z 548.8→170.0，IS [M+H]的前体离子优化到 m/z 472.2→436.2。兰瑞肽和 IS 的峰保留时间分别为 1.09 分钟和 1.22 分钟。狗血浆中的校准曲线样品浓度范围为 0.3 至 1000 ng/mL，线性良好，相关系数 r=0.9996。定量下限为 0.3 ng/mL。每个质控水平的日内和日间精密度（相对标准差）均<9.7%，准确度均<109.3%和<110.4%。兰瑞肽在狗血浆中各种条件下均稳定。皮下注射 Somatuline®（兰瑞肽）Autogel 120 mg 后雄性比格犬的兰瑞肽最大血浆浓度为 88.1 ng/mL。比格犬兰瑞肽的半衰期（T）较长，约为 198.6 h；从 0 到 840 h（第 35 天）的血浆浓度曲线下面积（AUC）为 6995 ng·h/mL。该 novel 定量方法采用 UPLC-MS/MS 成功应用于狗血浆中兰瑞肽的药代动力学分析。该结果将有助于未来药物制剂和再利用的研究。
