|
Lansoprazole (Lansoprazole) is a new type of proton pump inhibitors (proton pump inhib-itors, PPIs), after Omeprazole (Omeprazole), the second generation of the treatment of peptic ulcer drugs. Peptic ulcer is a frequently-occurring disease, common diseases, including gastric ulcer and duodenal ulcer. Excessive stomach acid, the mucosal protection weakened and H. pylori infection is the most important factor in producing ulcer disease. Therefore, the treatment of peptic ulcer drugs inhibit gastric acid secretion, anti-Helicobacter pylori, to protect the gastric mucosa. Proton pump inhibitors can block the gastric acid secretion in the last channel, this channel can inhibit basal gastric acid secretion and histamine, acetylcholine, gastrin and physical stimulation of acid secretion, is one of the basic measures for the treatment of peptic ulcer. Lansoprazole through fast and efficient inhibition of gastric acid secretion and clearing H. pylori achieve rapid cure ulcers. Objective: To establish a RP-HPLC (High Performance Liquid Chro-matography, HPLC) rapid and accurate determination of lansoprazole azole tablets in human plasma concentration determination methods. On this basis, the the Keyi forest (lansoprazole piece) as reference preparation, Wuhan Allianz Group IV drugs Pharmaceutical Co., Ltd. lansoprazole Yangtze River Pharmaceutical Group Sichuan Hairong Pharmaceutical Co., Ltd. tablets (test formulation) Pharmacokinetics and Bioequivalence evaluation reporting drug-related clinical data provide a scientific basis for the safety of the drug's clinical rational drug use and experimental data, but also for similar drugs The pharmacokinetic study provide a reference. Methods: The study is divided into two parts: the first part HPLC determination of lansoprazole concentration methodology to establish in human plasma. This part of the study include: column, mobile phase, flow rate, the internal standard, the detector such as the choice of processing methods, and the human plasma sample. The final selection of chromatographic conditions: Column: Agilent C 18 (250 mm × 5 mm, 5μm); mobile phase: acetonitrile 1 ‰ triethylamine (pH = 7.0) aqueous solution (v: v = 30: 70), a flow rate of 1.0 mL · min . -1 ; internal standard: omeprazole; injection volume: 20 μL; UV detection wavelength: 285 nm. At the same time, but also examines the analysis of the effect of the polarity of the modified C18 column lansoprazole. Human plasma sample processing methods: exact draw plasma sample, centrifuged, and the internal standard omeprazole, and basified, after centrifugation, the supernatant was dried with nitrogen. Added to the mobile phase, injection analysis. The second part of lansoprazole tablets with Jacuzzi forest in the bioequivalence study of the pharmacokinetics and biological in vivo single-dose oral administration in healthy subjects. Chemical drugs clinical pharmacokinetic study technology guiding principles \This test uses the internal standard method lansoprazole concentration of plasma samples was determined. The plasma concentration-time data via DAS 2.1.1 Pharmacokinetics Dynamics statistical software processing and with DAS2.1.1 statistical software for analysis of variance and two-sided t test (1-2α)% confidence interval analysis test tablets and reference whether the preparations are bioequivalent. The calculation of the other main pharmacokinetic parameters the T max the C max Found, AUC calculated by statistical moments. Results: In this experimental conditions, the HPLC theoretical plate number for 2360, the separation effect. Plasma lansoprazole and its baseline separation of high and higher selectivity, lansoprazole 50 to 2400 ng · mL -1 range a good linear relationship (r = 0.9992 , n = 6), the regression equation Y = -0.011320 0.000755X. The lowest limit of quantitation (LOQ) for 50 ng · mL -1 . Plasma extraction recoveries were in the low three concentrations (92.1, 11.7)%, (106.6, 14.3)% (108.2 11.2)%; the intraday precision RSD were 12.43%, 0.925% and 3.13%, respectively, during the day precision (RSD) were 9.27%, 6.99%, 4.81%, less than 15%. Freeze-thaw test at room temperature for 24 h and frozen 3d RSD were less than 10%. 2.20 cases of healthy male volunteers after a single dose oral test formulation of lansoprazole tablets and reference preparations Jacuzzi Lin 30 mg, T max , its main pharmacokinetic parameters were (2.52 ± 0.80) and (2.82 ± 0.69) h; C max / ng · mL -1 , respectively (854.82 ± 249.70) and (813.22 ± 289.59) ng · mL -1 ; AUC (0-12h) / μg · h · mL -1 (3779.90 ± 1191.52) and (3513.00 ± 742.25); the AUC (0 - ∞) / μg · h · mL -1 (3742.635 ± 749.854) (4078.542 ± 1171.173) ng · h -1 . T l/2Ka h / h, respectively (2.19 ± 0.49) and (2.38 ± 0.48). 3 main pharmacokinetic parameters of digital conversion, variance analysis, and the results show that the the two lansoprazole tablets AUC the (0-12h) the AUC (0 - ∞ ) , C max and T max showed no significant sex (P gt; 0.05), further double-sided t test (1-2α)% Confidence Interval Analysis the the AUC (0-12h) and C max ± There was no significant difference (P gt; 0.05), the test preparation AUC (0 - 12h) 90% confidence interval as reference preparation corresponding parameter of 88.4% to 103.8%, the C max 90% confidence interval of the corresponding parameter as reference preparation 92.2% to 127.2% . Conclusion: 1, HPLC analysis lansoprazole tablets pharmacokinetics and bioequivalence evaluation method (using C the 18 column), the method has a strong specificity, high detection sensitivity and accuracy of the results is good. All performance indicators are in line with the test requirements of the pharmacokinetics and bioequivalence studies. And the operation is simple, fast, high-precision and recovery. At the same time, the subject of the polarity the modified C 18 column lansoprazole analysis of preliminary research expected results. 2, the test on the test preparation (lansoprazole piece) and reference formulation were Bioequivalence evaluation examines the AUC 0 → ∞ , the AUC 0 → 12 < / sub> T 1/2 , the C max , and other indicators of the T max, over 2200 experimental data. The conclusion is: the two formulations are bioequivalent in healthy volunteers, the relative bioavailability of 95.8%, the two formulations were similar metabolic processes in the body, can be safe and effective in clinical use. 3, the test on the test preparation (lansoprazole piece) and reference formulation were pharmacokinetic studies to clarify the lansoprazole tablets in the human body absorption, distribution, metabolism and excretion of pharmacokinetic variation reporting to provide information for the drug dosing regimen to provide a scientific basis to guide the clinical development of safe, reasonable, and also provide a reference for similar drug development.
|