Antibiotic toxicity and absorption in zebrafish using liquid chromatography-tandem mass spectrometry.
Evaluation of drug toxicity is necessary for drug safety, but in vivo drug absorption is varied; therefore, a rapid, sensitive and reliable method for measuring drugs is needed. Zebrafish are acceptable drug toxicity screening models; we used these animals with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in a multiple reaction monitoring mode to quantify drug uptake in zebrafish to better estimate drug toxicity. Analytes were recovered from zebrafish homogenate by collecting supernatant. Measurements were confirmed for drugs in the range of 10-1,000 ng/mL. Four antibiotics with different polarities were tested to explore any correlation of drug polarity, absorption, and toxicity. Zebrafish at 3 days post-fertilization (dpf) absorbed more drug than those at 6 h post-fertilization (hpf), and different developmental periods appeared to be differentially sensitive to the same compound. By observing abnormal embryos and LD50 values, zebrafish embryos at 6 hpf were considered to be suitable for evaluating embryotoxicity. Also, larvae at 3 dpf were adapted to measure acute drug toxicity in adult mammals. Thus, we can exploit zebrafish to study drug toxicity and can reliably quantify drug uptake with LC-MS/MS. This approach will be helpful for future studies of toxicology in zebrafish.
National Institutes for Food and Drug Control, Graduate School of Peking Union Medical College, Beijing, China.
Fan
F
Zhang
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Graduate School of Peking Union Medical College, Beijing, China.
Wei
W
Qin
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Graduate School of Peking Union Medical College, Beijing, China.
Jing-Pu
JP
Zhang
National Institutes for Food and Drug Control, Graduate School of Peking Union Medical College, Beijing, China.
Chang-Qin
CQ
Hu
D065567:Absorption, Physiological / Q000187:drug effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D002823:Chorion; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004625:Embryo, Nonmammalian / Q000187:drug effects; D007928:Lethal Dose 50; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*
D000900:Anti-Bacterial Agents