Determination of the Polymers in Meropenem for Injection by Size Exclusion Chromatography(HPSCE) and Evaluation of Drug Quality / 中国药学杂志

OBJECTIVE: To establish a size exclusion chromatography(HPSCE) method for the determination of the polymers in meropenem for injection. METHODS: The analysis was carried out using a TSKgel G2000SWXL column(7.8 mm×30 cm, 5 μm). The mobile phase was pH 7.0 phosphate buffer solution(0.005 mol•L-1 disodium hydrogen orthophosphate-0.005 mol•L-1 sodium dihydrogen phosphate, 61:39, V/V). The flow rate was 0.8 mL•min-1. The detection wavelength was 254 nm. The column temperature was 25 ℃. RESULTS: The polymers were completely separated from meropenem. The calibration curve of meropenem was linear within the range of 2.54-50.83 μg•mL-1(r=0.999 6, n=6). The specificity of the HPSEC was checked by switching the effluent of each peak on the GFC to a C18 column and analyzing the effluent by LC-MS. CONCLUSION: This method is simple, accurate, sensitive, reliable and applicable for the determination of the polymers of meropenem, and can be applied to the drug quality evaluation.

Plasma protein binding characteristics of decapeptide in several species / 中国药学杂志

OBJECTIVE: To study the plasma protein binding rate of decapeptide in several species. METHODS: Ultrafiltration was employed to separate the free and bound decapeptide, acetonitrile was used to precipitate protein, then the plasma concentration of decapeptide by HPLC-MS/MS. RESULTS: The plasma protein binding rates of decapeptide at low, middle and high concentrations (50.0, 100.0, and 800.0 ng·mL-1) were (95.9±1.1)%, (97.40±0.7)% and (94.9±0.6)% in SD rats,(96.8±0.8)%, (97.8±0.2)% and (96.9±0.5)% in Beagle dogs, and (97.3±1.0)%, (98.6±0.2 )% and (96.2±0.9)% in humans, respectively. The average plasma protein binding rate was 96.2% after subcutaneous administration at 200 μg·kg-1 in SD rats. And the average plasma protein binding rate was 97.1% after intramuscular injection at 320 μg·kg-1 in Beagle dogs. CONCLUSION: Decapeptide has potent binding ability to plasma protein in several species. The plasma protein binding rate of decapeptide is independent of its plasma concentrations.

Plasma ibuprofen enantiomers and their pharmacokinetics in Beagle dogs determined by HPLC / 药学学报

A chiral high-performance liquid chromatography method was developed for the simultaneous determination of ibuprofen enantiomers in dog plasma. It was used to study the pharmacokinetics in the Beagle dog after intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen. Ketoprofen was chosen as the internal standard. After a simple precipitation using methanol as the precipitating solvent, both analytes and IS were separated on a Kromasil 100-5CHI-TBB chiral column (250 mm x4.6 mm, 5 μm) with isocratic elution using acetonitrile - 20 mmol x L(-1) phosphate buffer (pH 3.0, containing 5% methanol) (6 : 4) as the mobile phase. The detection wavelength was 220 nm. Liner calibration curves for both of the ibuprofen enantiomers were over the concentration range from 0.5 to 50 μg x mL(-1) with a lower limit of quantification of 0.5 μg x mL(-1), the accuracies were all in standard ranges. The intra- and inter- assay precisions were all below 7%. The recovery rate was 93.1% to 100.4%. The experiments proved that the method was simple, rapid and sensitive. It can be used in the quantitative determination of ibuprofen enantiomers in dog plasma. The method was used to determine the concentration of ibuprofen enantiomers in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen (9 mg x kg(-1)) and the pharmacokinetics parameters were calculated based on the concentration-time curves. The C(max) of S-ibuprofen in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen were 30.8 ± 4.7, 46.1 ± 5.9 and 20.0 ± 2.6 μg x mL(-1), respectively. In terms of the exposure of active ingredient, it revealed a significant difference between the administration of S-ibuprofen and the other two groups. The systematical R- to S- chiral inversion was discussed. Comparing the pharmacokinetic parameters at different doses, chiral inversion were 70.1% ± 36.6% and 76.4% ± 36.2%, respectively, after intravenous administration of racemic- and R-ibuprofen. This study provides a theoretical basis for the safety of ibuprofen formula of injection drug.

Research progress in receptor binding assay by mass spectrometry / 中国药学杂志

OBJECTIVE: To explain that receptor-ligand binding assay is an important drug screening method, which can quickly and inexpensively study the interactions between the targeted receptor and the potential ligands in vitro and provide information about the relative binding affinity of ligand-receptor. METHODS: The correlative literature and abroad were collected and analyzed. RESULTS AND CONCLUSION: The concept of MS binding assay based on mass spectrometric quantification of nonlabeled markers represents a promising alternative to conventional radioligands binding without inherent drawbacks. The technique will play an important role in the design and screening of receptor-targeting pharmaceuticals.

Determination of decapeptide LXT-101 in plasma by HPLC-MS/MS and its pharmacokinetics in Beagle dogs / 药学学报

This paper developed a sensitive and specific liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/MS) method for the determination of decapeptide LXT-101 in Beagle dog plasma. Plasma samples spiked with internal standard (IS) were treated with acetonitrile to precipitate the protein. Selected reaction monitoring (SRM) using the precursor --> product ion combinations of m/z 472.1-->587.9 and m/z 502.8-->633.8 were used to quantify LXT-101 and IS, respectively. The linear calibration curves were obtained in the concentration range of 0.5 - 500.0 ng x mL(-1). The limit of quantification (LOQ) was 0.5 ng x mL(-1). The inter-day and intra-day precision (RSD) across three validation run over the entire concentration range was below 10.9%, and the accuracy (RE) was within +/- 1.8%. The main pharmacokinetic parameters of LXT-101 after muscle injection of 20 microg x kg(-1) were as follows, AUC(0-t): (176.8 +/- 116.7) microg x h x L(-1), MRT(0-t): (2.52 +/- 0.53) h, T(1/2): (1.4 +/- 0.3) h; CL: (0.16 +/- 0.09) L x h(-1) x kg(-1), and Vd: (0.30 +/- 0.16) L x kg(-1), respectively. The method is proved to be specific, sensitive and suitable for the investigation of LXT-101 pharmacokinetics in Beagle dog.