Comparative Pharmacokinetics of Cinobufacini Capsule and Injection by UPLC-MS/MS.
Comparative Pharmacokinetics of Cinobufacini Capsule and Injection by UPLC-MS/MS.
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UPLC-MS/MS比较华蟾素胶囊与注射液的药代动力学
DOI：
10.3389/fphar.2022.944041
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发表时间：
2022
影响因子：
5.6
通讯作者：
Ding, Yue
中科院分区：
文献类型：
--
作者：
Li, Ming;Qin, Yanhong;Li, Zhe;Lan, Jinshuai;Zhang, Tong;Ding, Yue
华蟾素胶囊和注射剂是两种不同的同一来源的制剂，从中华大蟾蜍的皮肤中提取出来，已被中国国家食品药品监督管理局(CFDA)批准用于治疗各种癌症。我们先前的研究已经发现华蟾素胶囊和注射剂具有不同的抗癌作用，但它们不同的药代动力学行为可能导致这种情况的原因从未见过报道。因此，建立了一种灵敏、选择性地同时定量测定大鼠血浆中13种化合物的方法，该方法采用Agilent 6460型质谱仪，以多反应监测(MRM)的方式，对大鼠血浆中的13种化合物进行了同时定量。色谱柱为Agilent SB-C18柱，流动相为0.1%甲酸-乙腈，流速为0.3 mg/L/min，流速为0.3 mg/L。相关系数r为0.9967~0.9996，定量下限为0.2~4.84g/ml。该方法已被充分验证，并用于华蟾素胶囊和注射用大鼠体内的药动学差异研究。结果表明，给予华蟾素胶囊后，大鼠血浆中的9种成分均可被检测到，而华蟾素注射剂组仅检出蟾毒硫氨酸、蟾酥、华蟾素和伪蟾素。他们的药代动力学研究表明，端乙酰华蟾素、蟾酥、去乙酰华蟾素和华蟾素被预测为华蟾素胶囊的潜在活性物质，而蟾酥因其较高的血液药物暴露而被认为是华蟾素注射剂的主要成分。华蟾素胶囊3个不同剂量组的9种成分的AUC变化趋势相似，差异显著，且暴露剂量随剂量的增加而增加。华蟾素胶囊和注射剂中各主要成分的药代动力学特征差异较大，可以用来解释华蟾素胶囊和注射剂的药效差异，推测不同制剂的药效学成分。
Cinobufacini capsule and injection are two different formulations from the same source, obtained from the extraction of the skin of Bufo bufo gargarizans Cantor, which have been approved by the Chinese State Food and Drug Administration (CFDA) for the treatment of various cancers. Our previous study has found that the cinobufacini capsule and injection exhibited different anticancer effects, but their different pharmacokinetic behaviors, which could give a cause of that, have never been reported. So a sensitive and selective method for the simultaneous quantitation of 13 compounds in the rat plasma, including bufothionine, hellebrigenin, bufalin, gamabufotalin, telocinobufagin, cinobufagin, arenobufagin, cinobufotalin, desacetylcinobufotalin, bufotalin, pseudobufarenogin, resibufogenin, and desacetylcinobufagin, was established by using the Agilent 6460 mass spectrometer equipped with an ESI ion source in a multiple-reaction monitoring (MRM) mode. Chromatographic analysis was accomplished in 6 min by using an Agilent SB-C18 column and a mobile phase consisting of 0.1% formic acid in water and acetonitrile in an optimized gradient program at a flow rate of 0.3 ml/min. The correlation coefficients (r) of all analytes ranged from 0.9967 to 0.9996, while their lower limits of quantification ranged from 0.20 to 4.84 ng/ml. The method has been fully verified and applied for the pharmacokinetic difference study of the Cinobufacini capsule and injection in rats. The results showed that nine components could be quantitated in rat plasma samples after the administration of the cinobufacini capsule, while only bufothionine, bufalin, arenobufagin, and pseudobufarenogin could be detected in the cinobufacini injection group. Their pharmacokinetic studies indicated telocinobufagin, bufalin, desacetylcinobufagin, and arenobufagin were predicted as the potential active substances of the Cinobufacini capsule, while bufothionine was considered as a major ingredient in the cinobufacini injection due to its relatively high blood drug exposure. Also, the AUC of the nine components in cinobufacini capsule groups with three different doses showed a similar trend with significant differences, and the exposure increased with the increase of the dose. The pharmacokinetic characteristics of all major ingredients in cinobufacini capsules and injection were of wide variation, which could be used to explain differences in the efficacy of the cinobufacini capsule and injection and infer the pharmacodynamic ingredients of various cinobufacini preparations.
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DOI：
10.1155/2021/5596415
发表时间：
2021
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Peng W;Xu Y;Feng F;Gu C;Wang Z;Han D;Zhou X;He H
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影响因子：
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KAWAKAMI, M
影响因子：
3.1
作者：
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Bian, Baolin
影响因子：
5.7
作者：
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DOI：
10.1186/s13046-015-0134-9
发表时间：
2015-02-25
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
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