Simultaneous Determination of Purpurin, Munjistin and Mollugin in Rat Plasma by Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study after Oral Administration of Rubia cordifolia L. Extract.
A specific, simple, sensitive Ultra High Performance Liquid Chromatography-tandem Mass Spectrometry (UHPLC-MS/MS) method has been developed and validated for the simultaneous determination and pharmacokinetic study of purpurin, munjistin, and mollugin in rat plasma. Chromatographic separation was carried out using a C18 column (ACQUITY UPLC(®) HSS T3, 1.8 μm, 2.1 × 100 mm) with gradient elution. The compounds were detected on a 6430 triple-quadrupole tandem MS with an electrospray ionization (ESI) interface using multiple reaction monitoring (MRM) in positive ionization mode. The samples were prepared by a liquid-liquid extraction (LLE) method with ethyl acetate after being spiked with an internal standard (bifendate). The current UHPLC-MS/MS assay was validated for its linearity, intra-day and inter-day precisions, accuracy, extraction recovery, matrix effect and stability in different conditions. The method was linear for all analytes over the investigated range with all determined correlation coefficients exceeding 0.9900. The intra-day and inter-day precisions were in the range of 4.21% to 14.84%, and the relative errors of accuracies were in the range of -14.05% to 14.75%. The mean recoveries and matrix effects of purpurin, munjistin, and mollugin were higher than 78.87% and 92.56%, repectively. After oral administration of 0.82 g/kg of Rubia cordifolia extract, the maximum plasma concentrations (Cmax) were 70.10 ± 11.78 ng/mL for purpurin, 26.09 ± 6.6 ng/mL for munjistin, and 52.10 ± 6.71 ng/mL for mollugin. The time for maximal concentration (Tmax) was 1.61 ± 0.24 h for purpurin, 2.58 ± 0.19 h for munjistin, and 1.99 ± 0.21 h for mollugin. The established method was further applied to a pharmacokinetic study of purpurin, munjistin, and mollugin in rat plasma. It was concluded from the pharmacokinetic parameters that the three analytes showed a process of slow absorption and metabolism after oral administration of R. cordifolia extract to rats.
Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin 150081, Heilongjang, China. gaomingjie8888@163.com.
Mingjie
M
Gao
Analytical Department, Johnson &amp; Johnson, 199 Grandview Road, Skillman, NJ 08558, USA. jjsprite09@gmail.com.
Jing
J
Yang
Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, 24 Heping Road, Xiangfang District, Harbin 150040, Heilongjang, China. wzbmailbox@126.com.
Zhibin
Z
Wang
Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, 24 Heping Road, Xiangfang District, Harbin 150040, Heilongjang, China. ybywater@163.com.
Bingyou
B
Yang
Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, 24 Heping Road, Xiangfang District, Harbin 150040, Heilongjang, China. hxkuang@yahoo.com.
Haixue
H
Kuang
Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin 150081, Heilongjang, China. a1534064875@163.com.
Lu
L
Liu
Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin 150081, Heilongjang, China. wangliqian93@163.com.
Liqian
L
Wang
Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin 150081, Heilongjang, China. chunjuanyang@126.com.
Chunjuan
C
Yang
D000284:Administration, Oral; D000818:Animals; D000880:Anthraquinones / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D008297:Male; D015394:Molecular Structure; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D011714:Pyrans / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D015203:Reproducibility of Results; D045470:Rubia / Q000737:chemistry*; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry
D000880:Anthraquinones; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D011714:Pyrans; C046245:rubimaillin; C511975:purpurin anthraquinone
Rubia cordifolia L.; UHPLC-MS/MS; mollugin; munjistin; pharmacokinetics; purpurin