Biomedical subjects

Keliang Liu

Publications and source records attributed to Keliang Liu.

8 recordsLinked to original sources

PubMed2007

Biocompatible superparamagnetic iron oxide nanoparticle dispersions stabilized with poly(ethylene glycol)-oligo(aspartic acid) hybrids.

Methoxypoly(ethylene glycol)-oligo(aspartic acid) (MPEG-Asp(n)-NH(2), n = 2-5) hybrid block copolymers were synthesized and used as stabilizers to prepare superparamagnetic Fe(3)O(4) nanoparticles with magnetite as the inner core and and poly(ethylene glycol) as the hydrophilic outer shell. The aqueous dispersions of the nanoparticles were stable at pH 2-11 and in 1M NaCl solution, when repeat number, n, was 3 or more. Transmission electron microscopy showed that the nanoparticles, stabilized with MPEG-Asp(3)-NH(2), were about 14 nm in diameter. Magnetic measurements indicated that MPEG-Asp(3)-NH(2)-coated iron oxide nanoparticles showed superparamagnetic behavior. Cell adhesion assay and in vitro cell viability/cytotoxicity studies showed that MPEG-Asp(3)-NH(2)-coated iron oxide nanoparticles had less effect on cell adhesion/viability and morphology, and less cytotoxicity compared with uncoated, poly (acrylic acid)-coated, and MPEG-poly(acrylic acid)-coated iron oxide nanoparticles.

Animals↗

PubMed2006

In vivo characterization of a novel GnRH (gonadotropin-releasing hormone) antagonist, LXT-101, in normal male rats.

LXT-101 is a newly developed GnRH (gonadotropin-releasing hormone) analogue. In this study, the in vivo pharmacological profile in intact male rats and binding characters of LXT-101 were illustrated, and regulation of mRNA of hormone receptors related to the pituitary-gonadal axis during and after administration was observed to reveal its molecular mechanism of potent effect and reversibility. After single subcutaneous injections, LXT-101 produced a dose- and time-dependent suppression of serum testosterone level. Multiple administrations and osmotic pump implantation revealed that the time of onset and dose needed to maintain the effect of chemical castration decreased as the frequency of injection increased and gave direct proof that depot formulation could significantly improve the duration of antagonist delivery and pharmacological activities compared to the injectable formulation. And LXT-101 showed excellent character of regulating the pituitary-gonadal axis quickly and reversibly. Competitive binding assay showed that LXT-101 could specifically bind a pituitary GnRH receptor with high affinity. These results indicated that LXT-101 is fit for sustained-release formulation and it might possibly be developed as an ideal candidate for treating sex hormone-sensitive tumors and other disorders.

Animals↗

PubMed2006

Determination of penehyclidine by gas chromatographic-mass spectrometry and its application to pharmacokinetics in humans, rabbits and mice.

A sensitive and specific gas chromatographic-mass spectrometry with the extracted ion chromatograms (GC-MS/EIC) method has been developed and validated for the identification and quantification of penehyclidine (PH) in human and animal blood. The chromatography was on HP-5 capillary column (12 m x 0.2 mm x 0.3 microm). PH-d(5) was selected as the internal standard (IS). Simultaneous MS detection of PH and IS was performed at m/z 315 (PH) and m/z 320 (PH-d(5)), and the EIC of the two compounds was at 175 and 180. PH and PH-d(5) eluted at approximately 8.2 min and no endogenous materials interfered with their measurement. Linearity was obtained over the concentration range of 0.1-100 ng/ml in the blood. The lower limit of quantification (LLOQ) was reproducible at 50 pg/ml in both human and animal blood. The within-day and between-day precisions were no more than 9.1%. This method was successfully applied to quantification and pharmacokinetic studies of PH in the subjects. The concentration-time profiles of PH in humans, rabbits and mice were all fitted to first order absorption two-compartment open model after i.m. a single dose. The differences in absorption, distribution and elimination of PH among the species were found. The results provided the important information for developing a novel anti-cholinergic drug and for obtaining a more effectual remedy in clinical practice.

Adult↗

PubMed2006

Determination of thiencynonate by liquid chromatographic-mass spectrometry and its application to pharmacokinetics in rats.

A sensitive and specific high-performance liquid chromatography-tandem mass spectrometry method (LC/ESI/MS) was developed and validated for the identification and quantification of the novel lead compound of anticholinergic drug thiencynonate in rat plasma. The analytes were determined using positive electrospray ionization mass spectrometry in the selected reaction ion monitoring (SRM). The chromatography separation was on BetaBasic-18 column (150 mm x 2.1 mm i.d., 3 microm). The mobile phase was composed of methanol-water (70:30, v/v), containing 0.5 per thousand formic acid, which was pumped at a flow rate of 0.2 ml/min. Phencynonate was selected as the internal standard (IS). Simultaneous MS detection of thiencynonate and IS was performed at m/z 364.4 (thiencynonate), m/z 358 (phencynonate), and the SRM of the two compounds were both at 156. Thiencynonate eluted at approximately 2.8 min, phencynonate eluted at approximately 2.9 min and no endogenous materials interfered with their measurement. Linearity was obtained over the concentration range of 1-100 ng/ml in rat plasma. The lower limit of quantification (LLOQ) was reproducible at 1 ng/ml in rat plasma. The precision measured was obtained from 2.47 to 9.28% in rat plasma. Extraction recoveries were in the range of 67.63-76.76% in plasma. This method was successfully applied to the identification and quantification of thiencynonate in pharmacokinetic studies.

Administration, Oral↗

PubMed2005

Liquid chromatography-tandem mass spectrometry method for determination of phencynonate in rat blood and urine.

A sensitive and specific high-performance liquid chromatographic assay with electrospray ionization mass spectrometry detection (LC-ESI-MS) has been developed and validated for the identification and quantification of the novel anticholinergic drug phencynonate in rat blood and urine. The sample pretreatment involves basification and iterative liquid-liquid extraction with ethyl ether-dichloromethane (2:1, v/v) solution, followed by LC separation and positive electrospray ionization mass spectrometry detection. The chromatography was on BetaBasic-18 column (150 mm x 2.1mm i.d., 3 microm). The mobile phase was composed of methanol-water (85:15, v/v), containing 0.5 per thousand formic acid, which was pumped at a flow-rate of 0.2 ml/min. Thiencynonate was selected as the internal standard (IS). Simultaneous MS detection of phencynonate and IS was performed at m/z 358.4 (phencynonate), m/z 364 (thiencynonate), and the selected reaction ion monitoring (SRM) of the two compounds was at 156. Phencynonate eluted at approximately 5.25 min, thiencynonate eluted at approximately 5.10 min and no endogenous materials interfered with their measurement. Linearity was obtained over the concentration range of 1-100 ng/ml in rat blood and 1-500 ng/ml in rat urine. The lower limit of quantification (LLOQ) was reproducible at 1 ng/ml in both of rat blood and urine. The precision measured was obtained from 2.92 to 9.76% in rat blood and 4.17 to 9.76% in rat urine. Extraction recoveries were in the range of 69.57-79.49% in blood and 56.85-64.86% in urine. This method was successfully applied to the identification and quantification of phencynonate in pharmacokinetic studies.

Animals↗

PubMed2005

Chiral melamine derivatives: design, synthesis, and application to mass spectrometry-based chiral analysis.

A novel class of chiral melamine derivatives has been designed and synthesized. The ability of these compounds to perform chiral recognition toward 19 natural chiral alpha-amino acids has been investigated by electrospray ionization tandem mass spectrometry for the first time. The enantioselectivities of these new chiral selectors are encouraging. To elucidate some mechanism and regularity in the chiral recognition process using chiral melamine derivatives as chiral selectors, the effect of different noncovalent interactions caused by various chiral or achiral moieties in melamine derivatives on the chiral recognition in the gas phase has been studied at the same time. The result shows that electrostatic, hydrogen bond, pi-pi stacking, and steric interaction between selector and analyte play important roles in the association and enantioselective recognition of amino acids with the chiral melamine derivatives as chiral selectors. Enantiodiscrimination for analytes with different structures and properties could be improved by modifying substituents in melamine derivatives on purpose.

Amino Acids↗

PubMed2005

Chiral separation of anticholinergic drug enantiomers in nonaqueous capillary electrophoresis.

Nonaqueous capillary electrophoretic (NACE) method for the separation of nine structurally similar chiral anticholinergic drugs was developed. The eight drug enantiomers were separated on baseline within 18 min using 20mM phosphoric acid and 10 mM NaOH, containing 10 mM heptakis(2,3-dimethyl-6-sulfato)-4beta-cyclodextrin (HDMS-beta-CD) in methanol. The results were compared with those obtained in the high performance liquid chromatography system.

Cholinergic Antagonists↗

PubMed2002

NMR structure of a parallel-stranded DNA duplex at atomic resolution.

DNA dodecamers have been designed with two cytosines on each end and intervening A and T stretches, such that the oligomers have fully complementary A:T base pairs when aligned in the parallel orientation. Spectroscopic (UV, CD and IR), NMR and molecular dynamics studies have shown that oligomers having the sequences d(CCATAATTTACC) and d(CCTATTAAATCC) form a parallel-stranded duplex when dissolved at 1:1 stoichiometry in aqueous solution. This is due to the C:C+ clamps on either end and extensive mismatches in the antiparallel orientation. The structure is stable at neutral and acidic pH. At higher temperatures, the duplex melts into single strands in a highly cooperative fashion. All adenine, cytosine and thymine nucleotides adopt the anti conformation with respect to the glycosidic bond. The A:T base pairs form reverse Watson-Crick base pairs. The duplex shows base stacking and NOEs between the base protons T(H6)/A(H8) and the sugar protons (H1'/H2'/H2") of the preceding nucleotide, as has been observed in antiparallel duplexes. However, no NOEs are observed between base protons H2/H6/H8 of sequential nucleotides, though such NOEs are observed between T(CH3) and A(H8). A three-dimensional structure of the parallel-stranded duplex at atomic resolution has been obtained using molecular dynamics simulations under NMR constraints. The simulated structures have torsional angles very similar to those found in B-DNA duplexes, but the base stacking and helicoid parameters are significantly different.

Base Pairing↗