RESUMEN
This study established and validated an LC-MS/MS method for the ultrasensitive determination of cetagliptin in human plasma. Sample pretreatment was achieved by liquid-liquid extraction with ethyl acetate, and chromatographic separation was performed on an XB-C18 analytical column (50 × 2.1 mm, 5 µm) with gradient elution (0.1% formic acid in acetonitrile and 0.1% formic acid) at a flow rate of 1.0 mL/min. For mass spectrometric detection, multiple reaction monitoring was used, and the ion transitions monitored were m/z 421.2-86.0 for cetagliptin and m/z 424.2-88.0 for cetagliptin-d3. Method validation was performed according to the U.S. Food and Drug Administration Bioanalytical Method Validation Guidance, for which the calibration curve was linear in the range of 50.0-2000 pg/mL. All of the other results, such as selectivity, lower limit of quantitation, precision, accuracy, matrix effect, recovery, and stability, met the acceptance criteria. The validated method was successfully applied in a microdose clinical trial to systematically investigate the pharmacokinetic profile of cetagliptin in healthy subjects. Both rapid absorption and prolonged duration demonstrate the potential value of cetagliptin for diabetes treatment.
Asunto(s)
Cromatografía Liquida/métodos , Inhibidores de la Dipeptidil-Peptidasa IV/sangre , Espectrometría de Masas en Tándem/métodos , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Inhibidores de la Dipeptidil-Peptidasa IV/aislamiento & purificación , Inhibidores de la Dipeptidil-Peptidasa IV/farmacocinética , Humanos , Modelos Lineales , Extracción Líquido-Líquido , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: The efficacy and safety of Compound Kushen Injection (CKI) on advanced colon cancer remain controversial. We undertook a systematic meta-analysis of randomized controlled clinical studies on this issue. METHODS: A comprehensive literature search was conducted by searching the following electronic databases: PubMed, Cochrane, Chinese Biological Medical disc, Chinese National Knowledge Infrastructure, and Wan-Fang Database in China by the end of January 31, 2017, without language restriction. Meta-analysis was performed by using the random effects model to estimate the summary odd ratio (OR) with 95% confidence interval (CI) according to the study design. Stata 12.0 software was used for data analysis. The heterogeneity, sensitivity, and publication bias were assessed, respectively. RESULTS: A total of 14 trials met the inclusion criteria in present meta-analysis. The results suggested that CKI combined with chemotherapeutic drugs was favorable for the treatment of advanced colon cancer and could improve the patients' life quality. Funnel plot analysis and Egger's test suggested that there was not significant publication bias, and the sensitivity analysis indicated stable results. CONCLUSION: The current evidence suggested that CKI is favorable to improve the efficacy of chemotherapeutic drugs in patients with advanced colon cancer.
RESUMEN
Snake bile is one of the most expensive traditional Chinese medicines (TCMs). However, due to the complicated constitutes of snake bile and the poor ultraviolet absorbance of some trace bile acids (BAs), effective analysis methods for snake bile acids were still unavailable, making it difficult to solve adulteration problems. In present study, ultrahigh-performance liquid chromatography with triple quadrupole linear ion trap mass spectrometry (UHPLC-QqQ-MS/MS) was applied to conduct a quantitative analysis on snake BAs. The mass spectrometer was monitored in the negative ion mode, and multiple-reaction monitoring (MRM) program was used to determine the contents of BAs in snake bile. In all, 61 snake bile from 17 commonly used species of three families (Elapidae, Colubridae and Viperidae), along with five batches of commercial snake bile from four companies, were collected and detected. Nine components, Tauro-3α,12α-dihydroxy-7-oxo-5ß-cholenoic acid (T1), Tauro-3α,7α,12α,23R-tetrahydroxy-5ß-cholenoic acid (T2), taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), taurodeoxycholic acid (TDCA), cholic acid (CA), Tauro-3α,7α-dihydroxy-12-oxo-5ß-cholenoic acid (T3), and Tauro-3α,7α,9α,16α-tetrahydroxy-5ß-cholenoic acid (T4) were simultaneously and rapidly determined for the first time. In these BAs, T1 and T2, self-prepared with purity above 90%, were first reported with their quantitative determination, and the latter two (T3 and T4) were tentatively determined by quantitative analysis multi-components by single marker (QAMS) method for roughly estimating the components without reference. The developed method was validated with acceptable linearity (r2≥0.995), precision (RSDï¼6.5%) and recovery (RSDï¼7.5%). It turned out that the contents of BAs among different species were also significantly different; T1 was one of the principle bile acids in some common snake bile, and also was the characteristic one in Viperidae and Elapidae; T2 was the dominant components in Enhydris chinensis. This quantitative study of BAs in snake bile is a remarkable improvement for clarifying the bile acid compositions and evaluating the quality of snake bile.