Pharmacokinetics and Tissue Distribution of a Novel Bis-Chelated Gold(I) Diphosphine Compound, Bis(2,3-bis(tert-butylmethylphosphino)Quinoxaline)Aurate(I), in Rats
Ying Peng,
Huanhuan Qi,
Qingqing Chang,
Yu Zhang,
Weiyi Liu,
Minyu Liu,
Quanhai Liu,
Guangji Wang,
Jianguo Sun
Affiliations
Ying Peng
Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, China
Huanhuan Qi
Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, China
Qingqing Chang
Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, China
Yu Zhang
Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, China
Weiyi Liu
Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, China
Minyu Liu
Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, 1111 Zhong Shan Bei Yi Road, Shanghai 200437, China
Quanhai Liu
Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, 1111 Zhong Shan Bei Yi Road, Shanghai 200437, China
Guangji Wang
Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, China
Jianguo Sun
Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, China
GC20, a novel soluble bis-chelated gold(I)−diphosphine compound, has been reported as a promising anticancer candidate. Assessing the pharmacokinetic properties of GC20 is critical for its medicinal evaluation. First, a sensitive and specific liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed and well validated to determine GC20 in rat plasma and rat tissue homogenate after one step protein precipitation. Chromatographic separation was achieved on an Angilent ZORBAX-C18 column (3.5 μm, 2.1 × 50 mm) with gradient elution and mass spectrometry was performed on a triple quadrupole in positive ion mode using an electrospray ionization source. This method was then applied to investigate the pharmacokinetics and tissue distribution of GC20 in rats after intravenous administration. The results showed that the plasma exposure of GC20 in vivo increased with increasing doses after a single dose. However, after multiple doses, a significant accumulation and a saturation at elimination were observed for GC20 in rats. Moreover, after intravenous administration, GC20 was widely distributed in various tissues, with the highest levels in the lung, spleen, liver, and pancreas, followed by the kidney and heart, while the lowest level was found in the brain. This is the first report on the pharmacokinetic properties of GC20.
