Cicadae Periostracum (CP), the slough molted from the nymph of Cryptotympana pustulata, is a widely used medicinal material in traditional Chinese medicine (TCM). N-acetyldopamine oligomers (NAOs), the homologues of acetyldopamine, including N-acetyldopamine dimers/trimers/tetramers/pentamers (NADs/NATrs/NATes/NAPs), side-chain isomer of dimers/trimers (SCIDs/SCITrs), are major bioactive ingredients of CP. However, owing to commercially unavailable reference substances of all NAOs, simultaneous quantification of these NAOs in biological samples is difficult, and thus their pharmacokinetics are still unknown. In this study, a comprehensive strategy for simultaneous quantification/semi-quantification of NAOs in plasma with single N-acetyldopamine dimer A (NAD-A) as reference substance was established and comparatively investigated their pharmacokinetics after oral administration of pure NAD-A and two types of CP extracts, i.e., post-molting-washed slough (CP-WAT) and pre-molting-washed slough (CP-WBT). A UPLC-QTOF-MS/MS assisted UPLC-TQ-MS/MS strategy was developed to quantify NAOs in rat plasma. NAOs in CP extract were qualitatively characterized by UPLC-QTOF-MS/MS, then the quasi-molecular ions and characteristic fragment ions of the identified NAOs by UPLC-QTOF-MS/MS were transferred to UPLC-TQ-MS/MS as parent-daughter ion pairs for MRM mode quantification of the NAOs, and the method was validated with single NAD-A for quantifying NAD-A and semi-quantifying other NAOs in plasma. The established method was applied to compare the pharmacokinetics of NAOs after oral administration of NAD-A and the extracts of CP-WBT/CP-WAT respectively. Six quasi-molecular ions and characteristic fragment ion m/z 192.1 were characterized by UPLC-QTOF-MS/MS and transferred to be the parent-daughter ion pairs for UPLC-TQ-MS/MS analysis of six kinds of NAOs. For the pharmacokinetics, NAD-A showed double peaks absorption character when administered with single compound, but with higher relative bioavailability when administered with CP extracts with the similar dosage. Compared with CP-WAT, NAOs in CP-WBT reached the maximum plasma concentration in much shorter time.

蝉蜕（CP）是隐室蝉若虫蜕下的蜕皮，是中药中广泛使用的药材。N-乙酰多巴胺寡聚物（NAOs）是乙酰多巴胺的同系物，包括N-乙酰多巴胺二聚体/三聚体/四聚体/五聚体（NADs/NATrs/NATes/NAPs），二聚体/三聚体的侧链异构体（SCIDs/SCITrs） CP的生物活性成分。然而，由于商业上无法获得所有NAO的参考物质，因此很难同时定量生物样品中的这些NAO，因此它们的药代动力学仍然未知。在本研究中，采用单N对血浆中 NAO 进行同时定量/半定量的综合策略-建立乙酰多巴胺二聚体A（NAD-A）作为对照品，并比较研究口服纯NAD-A和两种类型的CP提取物（即蜕皮后水洗腐肉（CP-WAT）和预蜕皮后）后其药代动力学。蜕皮清洗腐肉（CP-WBT）。开发了 UPLC-QTOF-MS/MS 辅助 UPLC-TQ-MS/MS 策略来量化大鼠血浆中的 NAO。通过 UPLC-QTOF-MS/MS 对 CP 提取物中的 NAO 进行定性表征，然后用准-通过 UPLC-QTOF-MS/MS 鉴定的 NAO 的分子离子和特征碎片离子被转移到 UPLC-TQ-MS/MS 作为母子离子对，用于 NAO 的 MRM 模式定量，并且该方法通过单NAD-A 用于定量 NAD-A 并半定量血浆中的其他 NAO。应用建立的方法分别比较口服NAD-A和CP-WBT/CP-WAT提取物后NAOs的药代动力学。六种准分子离子和特征碎片离子m / z192.1 通过 UPLC-QTOF-MS/MS 进行表征，并转移为母子离子对，用于 6 种 NAO 的 UPLC-TQ-MS/MS 分析。药代动力学方面，NAD-A与单一化合物一起给药时表现出双峰吸收特征，但与相似剂量的CP提取物一起给药时具有更高的相对生物利用度。与CP-WAT相比，CP-WBT中的NAO在更短的时间内达到最大血浆浓度。