Validation of a HPLC-UV analytical and bioanalytical method for dexamethasone determination in nanoemulsions, porcine nasal mucosa, and mouse plasma and brain tissue

LC-MS/MS method for quantitation of gemcitabine and its metabolite 2′,2′-difluoro-2′-deoxyuridine in mouse plasma and brain tissue: Application to a preclinical pharmacokinetic study

High-performance liquid chromatographic method for the disposition of mazindol and its metabolite 2-(2-aminoethyl)-3-( p-chlorophenyl)-3-hydroxyphthalimidine in mouse brain and plasma

Determination of the enaminone DM5, an anti-epileptic agent, in mouse plasma and brain tissue by high-performance liquid chromatography with ultraviolet detection

Development and validation of GC–MS method for determination of methcathinone and its main metabolite in mice plasma and brain tissue after SPE: Pharmacokinetic and distribution study

A high-performance liquid chromatography method for temozolomide (TMZ) determination in complex biological matrices was developed and validated for application in in vitro, ex vivo and in vivo studies of new nanotechnology-based systems for TMZ nasal delivery. The method was able to quantify TMZ in nanoemulsions, following cellular uptake, in the porcine nasal mucosa and in mouse plasma and brain. Analyses were performed on a C18 column at 35°C, under UV detection at 330 nm. The mobile phase was methanol-acetic acid 0.5% (30:70, v/v), eluted at an isocratic flow rate of 1.1 mL/min. The method was found to be specific, precise, accurate, robust and linear (0.05 to 5 μg/mL) for TMZ determination in all matrices. No interference of TMZ degradation products was found under various stress conditions such as acidic, alkaline, oxidative, light and thermal exposure, demonstrating stability. The method was applied for the quantification of TMZ in different matrices, i.e. the efficiency of nanoemulsions in vitro in increasing TMZ cellular uptake, ex vivo TMZ permeation and retention in the porcine nasal mucosa tissue, and for in vivo TMZ quantification in mouse brain following intranasal nanoemulsion administration compared with free TMZ.

Validation of an HPLC-UV method for analysis of Kaempferol-loaded nanoemulsion and its application to in vitro and in vivo tests

Determination of pazopanib (GW-786034) in mouse plasma and brain tissue by liquid chromatography–tandem mass spectrometry (LC/MS–MS)

A rapid, sensitive, and simple gas chromatographic method with flame ionization detection is developed for the simultaneous determination of tetramethylpyrazine phosphate (TMPP) and borneol in mouse plasma and brain tissue. Sample preparations are carried out by deproteinization with an internal standard solution in methanol. The analytes and internal standard (dimethyl sulfoxide) are well-separated on an HP-5 MS capillary column. The analytical curves are linear over a wide concentration range of 0.02-40 microg/mL for both TMPP and borneol in plasma and brain tissue, with the intra- and inter-day precision (the relative standard deviation values) at less than 15%. TMPP and borneol are both stable under different conditions. The method described is successfully applied to the pharmacokinetic study of mouse plasma and brain tissue after oral administration of the Fufang TMPP and TMPP tablets to mice.

Compound 27 {1, 12-bis[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]dodecane-1,12-dione} is a novel small molecule agonist of EphA2 receptor tyrosine kinase. It showed much improved activity for the activation of EphA2 receptor compared with the parental compound doxazosin. To support further pharmacological and toxicological studies of the compound, a method using liquid chromatography and electrospray ionization tandem mass spectrometry (LC-MS/MS) has been developed for the quantification of this compound. Liquid-liquid extraction was used to extract the compound from mouse plasma and brain tissue homogenate. Reverse-phase chromatography with gradient elution was performed to separate compound 27 from the endogenous molecules in the matrix, followed by MS detection using positive ion multiple reaction monitoring mode. Multiple reaction monitoring transitions m/z 387.3 → 290.1 and m/z 384.1 → 247.1 were selected for monitoring compound 27 and internal standard prazosin, respectively. The linear calibration range was 2-200 ng/mL with the intra- and inter-day precision and accuracy within the acceptable range. This method was successfully applied to the quantitative analysis of compound 27 in mouse plasma and brain tissue with different drug administration routes.

Objective To investigate the effect of whole-body irradiation with low-dose γ-rays on the central nervous system of mice.Methods Fifty C57 mice were randomly divided into 3 groups and treated with 0,0.5,1 Gy whole-body irradiation,respectively.24 or 48 h after irradiation,brain tissue of mice was resected and homogenated.The levels of amino acid neurotransmitter,including Glu,Asp,GABA and Gly in brain homogenate were measured by high performance liquid chromatography (HPLC).Results Compared to the brain tissue of untreated mice,the contents of Glu and Asp at 0.5 and 1 Gy (t=-4.080,-3.935,-4.416,-3.630,-4.831, - 4.656,P ＜0.05) in mice brain tissue significantly increased at 24 h at 1 Gy and 48 h.However,the contents of Glu and Asp had no obvious changes in mice brain tissue 24 h after 1 Gy of irradiation. The contents of GABA and Gly had no difference between irradiated groups and untreated control group. Conclusions Short-term whole-body irradiation with low-dose γ-rays induces slight stimulation effect on the central nervous system of mice. Key words: γ-rays; Mice ; Low-dose irradiation ; Neurotransmitters

Sunitinib malate is a multi-targeted tyrosine-kinase inhibitor, currently in clinical trials for glioma. Previously developed methods for preclinical studies in species such as mice have either employed high-performance liquid chromatography (HPLC) or did not describe a detailed analytical method, which could be employed by other preclinical laboratories. In this paper, we have developed and validated a simple, sensitive high-performance liquid chromatography tandem mass-spectrometric method (LC-MS/MS) for the determination of sunitinib concentration in mouse plasma and brain tissue homogenate using dasatinib-free base as the internal standard. A single step liquid-liquid extraction method was used for both the matrices. Since sunitinib exhibits light-induced E/Z isomerism, all sample preparation was done in light-protected conditions. Separation was performed on a ZORBAX Eclipse XDB C18 column 4.6 × 50 mm, 1.8 μm. The mobile phase consisted of 20 mM ammonium formate (with 0.1 % formic acid): acetonitrile (70:30, v/v) pumped isocratically at a flow rate of 0.25 mL min-1 with a total run-time of 13 min. The retention times of sunitinib and dasatinib were 7.8 and 5.5 min, respectively. The calibration curve was linear over the range from 1.95 to 500 ng mL-1 in both plasma and brain tissue homogenate with 1.95 ng mL-1 as the lower limit of quantification (LLOQ) for both the matrices. Inter- and intra-day accuracy and precision was <15 % for low QC, med QC and high QC and <20 % for LLOQ. The method was applied to a pharmacokinetic study in FVB wild-type mice to determine the plasma and brain concentrations after a single oral sunitinib malate dose of 20 mg kg-1.

Sensitive liquid chromatography/mass spectrometry methods for quantification of pomalidomide in mouse plasma and brain tissue

A novel, simplified and stability-indicating high-throughput ultra-fast liquid chromatography method for the determination of rosmarinic acid in nanoemulsions, porcine skin and nasal mucosa

Determination of cediranib in mouse plasma and brain tissue using high-performance liquid chromatography–mass spectrometry

To investigate the development and dynamic changes of cysts in the brain of mice following infection with different forms of Toxoplasma gondii, so as to provide insights into for toxoplasmosis prevention and control. ICR mice at ages of 6 to 8 weeks, each weighing 20 to 25 g, were intraperitoneally injected with tachyzoites of the T. gondii PRU strain at a dose of 1 × 105 tachyzoites per mouse, orally administered with cysts at a dose of 20 oocysts per mouse or oocysts at a dose of 200 oocysts per mouse for modeling chronic T. gondii infection in mice, and the clinical symptoms and survival of mice were observed post-infection. Mice were orally infected with T. gondii cysts at doses of 10 (low-dose group), 20 (medium-dose group), 40 cysts per mouse (high-dose group), and the effect of different doses of T. gondii infections on the number of cysts was examined in the mouse brain. Mice were orally administered with T. gondii cysts at a dose of 20 cysts per mouse, and grouped according to gender (female and male) and time points of infections (20, 30, 60, 90, 120, 150, 180 days post-infection), and the effects of gender and time points of infections on the number of cysts was examined in the mouse brain. In addition, mice were divided into the tachyzoite group (Group T), the first-generation cyst group (Group C1), the second-generation cyst group (Group C2), the third-generation cyst (Group C3) and the fourth-generation cyst group (Group C4). Mice in the Group T were intraperitoneally injected with T. gondii tachyzoites at a dose of 1 × 105 tachyzoites per mouse, and the cysts were collected from the mouse brain tissues 30 days post-infection, while mice in the Group C1 were orally infected with the collected cysts at a dose of 30 cysts per mouse. Continuous passage was performed by oral administration with cysts produced by the previous generation in mice, and the effect of continuous passage on the number of cysts was examined in the mouse brain. Following infection with T. gondii tachyzoites, cysts and oocysts in mice, obvious clinical symptoms were observed on days 6 to 13 and mice frequently died on days 7 to 12. The survival rates of mice were 67.0%, 87.0% and 53.0%, and the mean numbers of cysts were (516.0 ± 257.2), (1 203.0 ± 502.0) and (581.0 ± 183.1) in the mouse brain (F = 11.94, P < 0.01) on day 30 post-infection with T. gondii tachyzoites, cysts and oocysts, respectively, and the numbers of cysts in the brain tissues were significantly lower in mice infected with T. gondii tachyzoites and oocysts than in those infected with cysts (all P values < 0.01). The survival rates of mice were 87.0%, 87.0% and 60.0%, and the mean numbers of cysts were (953.0 ± 355.5), (1 084.0 ± 474.3) and (1 113.0 ± 546.0) in the mouse brain in the low-, medium- and high-dose groups on day 30 post-infection, respectively (F = 0.42, P > 0.05). The survival rates of male and female mice were 73.0% and 80.0%, and the mean numbers of cysts were (946.4 ± 411.4) and (932.1 ± 322.4) in the brain tissues of male and female mice, respectively (F = 1.63, P > 0.05). Following continuous passage, the mean numbers of cysts were (516.0 ± 257.2), (1 203.0 ± 502.0), (896.8 ± 332.3), (782.5 ± 423.9) and (829.2 ± 306.0) in the brain tissues of mice in the T, C1, C2, C3 and C4 groups, respectively (F = 4.82, P < 0.01), and the number of cysts was higher in the mouse brain in Group 1 than in Group T (P < 0.01). Following oral administration of 20 T. gondii cysts in mice, cysts were found in the moues brain for the first time on day 20 post-infection, and the number of cysts gradually increased over time, peaked on days 30 and 90 post-infection and then gradually decreased; however, the cysts were still found in the mouse brain on day 180 post-infection. There is a higher possibility of developing chronic T. gondii infection in mice following infection with cysts than with oocysts or tachyzoites and the most severe chronic infection is seen following infection with cysts. The number of cysts does not correlate with the severity of chronic T. gondii infection, and the number of cysts peaks in the mouse brain on days 30 and 90 post-infection.