We have developed a series of new C10 dipeptide stationary phases via a simple and effective synthetic method. The preparation of the new phases involves the synthesis of silanes and the surface modification of silica. Chromatographic evaluations of these columns were performed using the Engelhardt, Tanaka, and Neue test mixtures. The applicability of these new stationary phases was also evaluated using a series of diagnostic probes including acids, bases or neutral compounds and several generic applications. These new C10 dipeptide stationary phases showed excellent hydrolytic stability over a wide pH range. Like other existing amide-embedded columns, these new stationary phases exhibit higher retention for polar and hydrophilic compounds and different selectivity as compared to conventional C18 columns. These new phases are compatible with 100% aqueous mobile phases, and also provide high column efficiency and good peak shapes for both acidic and basic compounds.Highlights► New C10 dipeptide stationary phases were developed via an effective method. ► Chromatographic parameters were evaluated. ► The new stationary phases exhibit good properties for applications in RPLC. ► The new stationary phases are a useful complement to conventional C18 columns.

Sometimes, drugs and their metabolites in plasma may convert to each other. This phenomenon is called interconversion, which may result in the instability problem of the plasma samples. The instability problem caused by interconversion of the co-existing metabolites may often be ignored, since there is no drug metabolite in the quality control samples prepared for method validation. Pitavastatin lactone (Pi-LAC), a main metabolite of pitavastatin (Pi), is very unstable and easily converted to Pi in plasma. In this paper, simple and rapid LC-ESI-MS/MS methods were developed for the simultaneous determination of Pi and Pi-LAC in human plasma and urine. The sample stability was examined under different conditions. The interconversion of Pi and Pi-LAC was prevented by adding a pH 4.2 buffer solution to the freshly collected plasma samples. Detection was performed using an electrospray ionization (ESI) operating in positive ion multiple reaction monitoring mode by monitoring the ion transitions from m/z 422.2→290.3 (Pi), 404.2→290.3 (Pi-LAC) and m/z 611.3→423.2 (candesartan cilextetil, the internal standard), respectively. The calibration curve of Pi and Pi-LAC in both human plasma and urine showed good linearity over the concentration range of 0.1–200 ng/mL. The established methods were successfully applied to a pharmacokinetic study of pitavastatin calcium tablets in healthy Chinese volunteers after oral administration of 1, 2 and 4 mg single and multiple doses of pitavastatin calcium. The pharmacokinetic parameters of Pi and Pi-LAC in Chinese volunteers were given respectively. The urinary excretion profiles of Pi and Pi-LAC in Chinese volunteers were also presented. After receiving a single 4 mg oral dose of pitavastatin calcium, the average cumulative urinary excretion percentages of Pi and Pi-LAC in Chinese volunteers were (0.41 ± 0.16)% and (6.1 ± 5.0)%, respectively.

The modernization and marketing of traditional Chinese medicine is difficult primarily because its pharmacodynamic material basis has not been elucidated. Moreover, a central problem is the lack of effective research methods and strategies. After >20 years of study, here, we propose the theory of pharmacodynamic differential serum chromatography. The method described here can be used to identify (and possibly develop) effective pharmacodynamic materials. In light of the theory, we identified hydroxysafflor yellow A (HSYA) to be the effective pharmacodynamic material of Carthamus tinctorius L. (safflower). With the help of the methodology described here, the modernization and understanding of traditional Chinese medicine may be accelerated.

A multivalent fusion vaccine is a promising option for protection against Helicobacter pylori infection. In this study, UreB414 was identified as an antigenic fragment of urease B subunit (UreB) and it induced an antibody inhibiting urease activity. Immunization with UreB414 partially protected mice from H. pylori infection. Furthermore, a trivalent fusion vaccine was constructed by genetically linking heat shock protein A (HspA), H. pylori adhesin A (HpaA), and UreB414, resulting in recombinant HspA-HpaA-UreB414 (rHHU). Its protective effect against H. pylori infection was tested in BALB/c mice. Oral administration of rHHU significantly protected mice from H. pylori infection, which was associated with H. pylori-specific antibody production and Th1/Th2-type immune responses. The results show that a trivalent fusion vaccine efficiently combats H. pylori infection, and that an antigenic fragment of the protein can be used instead of the whole protein to construct a multivalent vaccine.

Hydroxysafflor yellow A (HSYA) is a component of the flower Carthamus tinctorius L. that elicits neuroprotective effects in vivo and in vitro. The purpose of this study was to investigate pharmacological properties of HSYA on neurotoxicity of glutamate in primary cultured rat cortical neurons along with its possible mechanism of action. After challenge with N-methyl-d-aspartate (NMDA, 100 μM) for 30 min, loss of cell viability and excessive apoptotic cell death were observed in cultured cortical neurons. However, the excitotoxic neuronal death was attenuated markedly by HSYA treatment. Western blot analysis revealed that HSYA decreased expression of Bax and rescued the balance of pro-and anti-apoptotic proteins. In addition, HSYA significantly reversed up-regulation of NR2B-containing NMDA receptors by exposure to NMDA, while it did not affect the expression of NR2A-containing NMDA receptors. These finding suggest that HSYA protects cortical neurons, at least partially, from inhibiting the expression NR2B-containing NMDA receptors and by regulating Bcl-2 family.

Background: Lansoprazole, a benzimidazole derivative, is indicated for the treatment of various peptic diseases. It is metabolized mainly in the liver, and its primary active metabolites present in plasma are 5′-hydroxy lansoprazole and lansoprazole sulfone. Few data are available on the pharmacokinetic properties of lansoprazole, 5′-hydroxy lansoprazole, and lansoprazole sulfone, which can be used to measure cytochrome P450 (CYP) 2C19 activity.Objectives: The aims of this study were to investigate the clinical plasma pharmacokinetic properties of lansoprazole and its metabolites in healthy Chinese male volunteers, and to assess the influences of CYP2C19 on the pharmacokinetics of lansoprazole.Methods: Healthy adult Chinese male volunteers were enrolled in this single-dose, open-label study. All patients received a single oral enteric capsule containing 30 mg of lansoprazole after a 12-hour overnight fast. Serial blood samples were collected immediately before (0 hour) and at 20, 40, 60, 90, 120, and 150 minutes and 3, 4, 6, 8, 10, 12, 15, and 24 hours after study drug administration. The plasma concentrations of lansoprazole, 5′-hydroxy lansoprazole, and lansoprazole sulfone were determined using a validated internal standard high-performance liquid chromatography—tandem mass spectrometry (HPLC-MS/MS) method. Pharmacokinetic properties (including Cmax, Tmax, elimination t½ [t½z], mean residence time [MRT], AUC0–24, AUC0−∞, apparent oral clearance [CLz/F], and apparent volume of distribution [Vz/F]) were determined using the noncompartmental method.Results: Twenty volunteers (mean [SD] age, 34.9 [2.9] years; weight, 64.6 [2.2] kg; height, 171.3 [3.3] cm) were enrolled in and completed the study. The mean (SD) pharmacokinetic properties of lansoprazole were as follows: Cmax, 1047 (344) ng/mL; Tmax, 2.0 (0.7) hours; t½z, 2.24 (1.43) hours; MRT, 3.62 (0.87) hours; AUC0−24, 3388 (1484) ng/mL/h; AUC0-∞, 3496 (1693) ng/mL/h; CLz/F, 9.96 (3.74) L/h; and Vz/F, 32.83 (11.74) L. The findings with 5′-hydroxy lansoprazole and lansoprazole sulfone, respectively, were as follows: Cmax, 111.2 (41.8) and 66.6 (52.9) ng/mL; Tmax, 2.1 (0.8) and 1.9 (0.8) hours; t½z, 2.31 (1.18) and 2.52 (1.54) hours; and AUC0−24, 317.0 (81.2) and 231.9 (241.7) ng/mL/h. No adverse events were reported throughout the study.Conclusions: In these healthy Chinese male volunteers administered a single oral dose of lansoprazole 30 mg, absorption of lansoprazole was rapid (mean Cmax, 1047 ng/mL; Tmax, ~2.0 hours). Its 2 primary active metabolites, 5′-hydroxy lansoprazole and lansoprazole sulfone, were identified in measurable quantities in plasma (Cmax, 111.2 and 66.6 ng/mL, respectively; and Tmax, 2.1 and 1.9 hours). The plasma t½z did not appear to reflect the duration of suppression of gastric acid secretion: the t½z values of lansoprazole and the 2 metabolites were ~2 to 2.5 hours, while the acid-inhibitory effect lasted >24 hours. Cmax, AUC, and t½z of lansoprazole, and especially lansoprazole sulfone, varied. Differences in metabolism types and/or genotype of CYP2C19 should be taken into account when planning a lansoprazole dosing regimen.

•Associations between vancomycin treatment and nephrotoxicity were evaluated retrospectively in 90 patients in the northwest of China.•Fourteen (15.6%) patients developed nephrotoxicity, with serum creatinine elevated significantly from mean (standard deviation) 90.0 (18.8) μmol/l to 133.8 (63.2) μmol/l (p = 0.015).•Drug dosing >38 mg/kg/day and a serum trough level >20 mg/l were identified as risk factors of nephrotoxicity.•The renal function of critically ill patients receiving vancomycin should be monitored closely.ObjectiveTo identify specific risk factors of vancomycin-induced nephrotoxicity in China, as the relationship between vancomycin therapy (dosing and trough concentration monitoring) and nephrotoxicity has been the subject of critical debate.MethodsThe cases of 90 critically ill patients who received vancomycin therapy in Xijing Hospital in the northwest of China between March 2014 and January 2015 were reviewed retrospectively. Vancomycin dosing, blood serum trough concentration, and other independent risk factors associated with nephrotoxicity were evaluated in a multivariable model.ResultsAmong the 90 critically ill patients, 59 were males; mean age was 46.3 years. The indications for vancomycin use were methicillin-resistant Staphylococcus aureus-associated pneumonia, central nervous system infection, and bacteremia. Clinical pharmacists prescribed weight-based dosing, ranging from 20 to 45 mg/kg/day. Fourteen (15.6%) patients developed nephrotoxicity, with serum creatinine elevated significantly from a mean (standard deviation) of 90.0 (18.8) μmol/l to 133.8 (63.2) μmol/l (p = 0.015). It was found that those with a vancomycin dosage >38 mg/kg/day (50.0% vs. 11.3%, p = 0.004) and a vancomycin serum trough concentration >20 mg/l (57.1% vs. 12.0%, p = 0.01) were more likely to develop nephrotoxicity.ConclusionThe data from this study indicate that a vancomycin dosage >38 mg/kg/day and a serum trough level >20 mg/l are both independent factors associated with the development of nephrotoxicity, suggesting that renal function should be monitored closely during vancomycin treatment.