A new designed hybrid peptide FSH33-53-Lytic was synthesized and expected to combine the follicle stimulating hormone receptor (FSHR) targeting and tumor cell membranes disintegration. Through in vitro and vivo study, no significant enhancement on anti-tumor activity was shown compared with Lytic peptide only. We also prepared 18F-Al-NOTA-MAL-FSH33-53-Lytic and use microPET image to observe the FSHR targeting of FSH33-53-Lytic. No accumulation in the tumor may explain the failure of FSH33-53-Lytic on cancer therapy. In summary, microPET image can provide more accurate and visible information for screening new anti-tumor agents.

•The determination of Aucubin, Ajugol and Catalpol in rat plasma and tissue by LC–MS/MS.•The LLOQ for three analytes is 1 ng/mL in all biological fluids.•The method was used to a preclinical pharmacokinetics and tissue distribution study.•Higher level of Aucubin, Ajugol and Catalpol were found in kidney tissue.•Aucubin and Catalpol could cross the blood–brain barrier.To enable an investigation of pharmacokinetics and tissue distribution of Aucubin, Ajugol and Catalpol in rats, a high-performance liquid chromatography–electro spray ionization tandem mass spectrometry (HPLC–ESI–MS/MS) method was developed for the simultaneous quantitative determination of the three compounds. Biological samples were prepared by a simple protein precipitation with methanol (containing 0.05% formic acid). The analytes were separated by a C18 reversed phase column and detected with a triple quadrupole tandem mass spectrometer in the multiple-reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 364.3 → 149.0 for Aucubin, m/z 366.5 → 151.1 for Ajugol, m/z 380.0 → 183.3 for Catalpol and m/z 530.3 → 183.1 for Picroside-II (IS) in positive ionization. Good linearity of each calibration curve was produced over the concentration range of 1–1000 ng/mL. The lower limit of quantification (LLOQ) was 1 ng/mL for the three analytes. This method was successfully applied to the pharmacokinetic and tissue distribution studies of Aucubin, Ajugol and Catalpol in rat. The current results revealed pharmacokinetic behaviors of the herb compound and provided novel evidence of the presence of Aucubin and Catalpol in rat brain. The acquired data would be helpful for the clinical application and further studies of Traditional Chinese Medicines (TCM) with active ingredients of Iridoid Glycosides.

To establish a rapid and sensitive ultra performance liquid chromatography mass spectrometry (UPLC–MS/MS) method for the determination of concentration of guanfu base G (GFG) and its active metabolites in rat plasma. The GFG and its active metabolites and the internal standard (phenacetin) were separated on an Acquity UPLC® BEH C18 chromatography column (2.1 mm × 50 mm I.D., 1.7 μm) using gradient elution with a mobile phase of methanol and ultrapure water at a flow rate of 0.4 mL/min. The detection was performed on a Xevo triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 472.26 → m/z 310.03 for GFG and m/z 180.00 → m/z 109.99 for phenacetin (IS) using a positive electrospray ionization interface. The lower limit of quantification (LLOQ) was 1 ng/mL, the limit of detection (LOD) was 0.3 ng/mL, and the linear calibration curve was obtained over the concentration range of 1–200 ng/mL. The intra-day and inter-day assay variations were measured to be below 10.97%, and the accuracy values (relative error) ranged from 95.4% to 103.6%. After validation, this method was successfully applied to a pharmacokinetic study where rats were intravenous administration of 5 mg/kg GFG. A simple, rapid, sensitive, and accurate method for the determination of the concentration of GFG and its metabolites in rat plasma was developed and validated.

•A new RPIC method for the determination of antazoline hydrochloride is developed.•Concentration of antazoline hydrochloride in biological sample is determined.•The pharmacokinetic characteristic of antazoline hydrochloride in dog is studied.•t1/2 result shows higher therapy compliance of our drug for further study in patient.In order to evaluate the pharmacokinetics characteristic of antazoline hydrochloride in Beagle dogs, a sensitive and specific HPLC method was developed and validated using phenacetin as the internal standard (IS). The analyte and the IS were extracted from dog plasma by ethyl acetate under the basic condition. The analyte was separated by a C18 column and detected with a variable wavelength UV-detector. The mobile phase consisted of methanol–5 mmol L−1 tetrabutyl ammonium bromide (45:55, v/v) containing 0.5% glacial acetic acid in a flow rate of 1.0 mL min−1. Standard calibration graph for antazoline was linear over a curve range of 20–1600 ng mL−1 (R > 0.99) and the lower limit of quantification was 20 ng mL−1 using a plasma sample of 500 μL. The intra- and inter-day precision values were less than 14.3% relative standard deviation (RSD). The intra-day assay accuracy was in the range of 98.1–100.6% and the inter-day assay accuracy in the range of 99.2–101.1%. The extraction recoveries were on the average of 88.4% for antazoline and 76.8% for IS. Plasma samples were stable at least for 1 month at −20 °C. This method was successfully applied to pharmacokinetics study of antazoline after intravenous administration to Beagle dogs.

Melanin, a natural biological pigment present in many organisms, has been found to exhibit multiple functions. An important property of melanin is its ability to chelate metal ions strongly, which might be developed as an iron chelator for iron overload therapy. Herein, we prepared the ultrasmall water-soluble melanin nanoparticle (MP) and firstly evaluate the pharmacokinetics of MP in iron-overload mice to provide scientific basis for treating iron-overload. To study the circulation time and biodistribution, MP was labeled with 89Zr, a long half-life (78.4 h) positron-emitting metal which is suited for the labeling of nanoparticles and large bioactive molecule. MP was chelated with 89Zr directly at pH 5, resulting in non-decay-corrected yield of 89.6% and a radiochemical purity of more than 98%. The specific activity was at least190 MBq/μmol. The 89Zr-MP was stable in human plasma and PBS for at least 48 h. The half-life of 89Zr-MP was about 15.70 ± 1.74 h in iron-overload mice. Biodistribution studies and MicroPET imaging showed that 89Zr-MP mainly accumulated in liver and spleen, which are the target organ of iron-overload. The results indicate that the melanin nanoparticle is promising for further iron overload therapy.