Comparative pharmacokinetic study of pyranocoumarins and khellactone in normal and acute lung injury rats after oral administration of Peucedanum praeruptorum Dunn extracts using a rapid and sensitive liquid chromatography-tandem mass spectrometry method.
Pyranocoumarins are the main constitutes in Peucedanum praeruptorum Dunn and possess various biological activities. In this article, we developed and validated a rapid and sensitive liquid chromatography-tandem mass spectrometry method for the targeted quantification of the pyranocoumarins, praeruptorin A, praeruptorin B and praeruptorin E, and khellactone, which is a common metabolite of these pyranocoumarins in rat plasma samples. We then performed a comparative pharmacokinetic study of these pyranocoumarins and khellactone in normal and lipopolysaccharide-induced acute lung injury (ALI) in rats following oral administration of P. praeruptorum Dunn extracts. Calibration curves gave desirable linearity (r > 0.99) and the lower limit of quantifications were sufficient for quantitative analysis. The precision and accuracy were assessed by intra-batch and inter-batch assays, and the relative standard deviations were all within 10.23% and the accuracy (relative error) was between -5.52% and 8.68%. The extraction recoveries, matrix effects and stability were also acceptable. The pharmacokinetic study revealed that the area under the concentration-time curve (0-t) of khellactone in ALI rats was significantly decreased compared with the normal rats. Meanwhile, the systemic exposures of these pyranocoumarins were slightly higher in the ALI rats than those in normal rats were. The pharmacokinetic study in the pathological state might provide information that was more comprehensive to guide the clinical usage of P. praeruptorum Dunn.
Jiangsu Key Laboratory of Pediatric Respiratory Disease, State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing, China.|Key Laboratory for Functional Substance of Chinese Medicine, Nanjing, China.
An
http://orcid.org/0000-0003-1555-6063
A
Kang
Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Tong
T
Xie
Jiangsu Key Laboratory of Pediatric Respiratory Disease, State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing, China.
Dong
D
Zhu
Jiangsu Key Laboratory of Pediatric Respiratory Disease, State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing, China.
Yu
Y
Dong
Jiangsu Key Laboratory of Pediatric Respiratory Disease, State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing, China.
Hongmei
H
Wen
Jiangsu Key Laboratory of Pediatric Respiratory Disease, State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing, China.
Yuqiong
Y
Pei
Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.|Key Laboratory for Functional Substance of Chinese Medicine, Nanjing, China.
Jinjun
J
Shan
Jiangsu Key Laboratory of Pediatric Respiratory Disease, State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing, China.|Key Laboratory for Functional Substance of Chinese Medicine, Nanjing, China.
Liuqing
L
Di
D055371:Acute Lung Injury / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D003374:Coumarins / Q000032:analysis / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D057230:Limit of Detection; D016014:Linear Models; D008168:Lung / Q000737:chemistry; D008297:Male; D039681:Pyranocoumarins / Q000032:analysis / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
D003374:Coumarins; D004365:Drugs, Chinese Herbal; D039681:Pyranocoumarins; C520900:khellactone
Peucedanum praeruptorum Dunn; liquid chromatography-tandem mass spectrometry; pharmacokinetics; pyranocoumarins