ABSTRACT
@#Overactive bladder is a syndrome characterized by urgent urination, often accompanied by frequent urination and nocturia. The incidence of the disease is high all over the world, and it has a great impact on the lives of patients, which has been paid more and more attention by scholars at home and abroad. It is currently estimated that 50 million to 100 million people worldwide suffer from the disease. Mirabegron is an agonist of human β-3 adrenergic receptor used to treat symptoms of overactive bladder. In this study, the synthesis process of mirabegron was improved based on literatures. Using p-nitrophenethylamine hydrochloride, R-(-)-mandelicacid and 2-aminothiazole-4-acetic acid as starting materials, the target product with high purity was obtained through four steps of amide condensation, carbonyl reduction, nitro reduction and amide condensation, and one-step purification, with a total yield of 39%. In this study, the hydrogen source of nitro reduction in step 3 was changed from hydrogen to ammonium formate, which increased the feasibility of industrialization, and mirabegron was refined to improve the purity of the product. The improved process has the advantages of simplified operation and mild reaction conditions, which provides a new method for the preparation and purification of mirabegron.
ABSTRACT
@#A sensitive and selective method for the determination of imidafenacin in human plasma using liquid chromatography combined with mass spectrometry was established, and was applied to the pharmacokinetic and bioequivalence studies of imidafenacin in healthy Chinese volunteers. After the liquid-liquid extraction pretreatment, samples were separated by UPLC on BEH C8(2. 1 mm×50 mm, 1. 7 μm)column with mobile phase 2 mmol/L ammonium acetate solution with 0. 2% acetic acid and acetonitrile using gradient elution. The mass instrument was operated in the positive ion mode, and the monitored transition was set at m/z 320. 2→238. 1 and m/z 330. 2→248. 2 for imidafenacin and IS(imidafenacin-d10), respectively. In the single-dose, double cycle, self-crossover clinical trial, 24 healthy Chinese volunteers received 0. 1 mg reference or test imidafenacin tablet orally under fasting condition. Drug concentration in plasma was determined by this method and the pharmacokinetic parameters were calculated by DAS 3. 2. 8 software. The linear range of the analysis method is 10. 0 pg/mL to 1 000 pg/mL. The extraction recoveries of the low medium and high concentration samples were 84. 0%, 88. 0% and 90. 0%, respectively. The matrix effects of low medium and high concentration samples were 105%, 100% and 101%, respectively. The pharmacokinetic parameters of imidafenacin for the reference and test tablets were as follows: cmax 524. 8 pg/mL vs 612. 6 pg/mL, tmax 1. 250 h vs 1. 063 h, AUC0-∞ 2 229 pg ·h/mL vs 2 466 pg ·h/mL. The reference and test tablets of imidafenacin were bioequivalent. This method proved to be rapid and accurate for the pharmacokinetic and bioequivalence studies of imidafenacin.
ABSTRACT
Objective: To establish the fingerprint of Danshen Glucose Injection by HPLC. Methods: Separation was performed on an Alltima C18(4.6mm?250mm,5?m) analytical column, with mobile phase consisting of 1 %acetic-water and 1 %acetic acid-methanol and with gradient elute at the flow rate of 1mL/min-1. The UV detection was set at 281nm. Results: Six peaks of Danshen Glucose Injection wre indicated, and the chief ingredients were determined by HPLC. Conclusion: This method is accurate and with good reproducibility and can be used for the quality control of Danshen Glucose Injection.
ABSTRACT
Object To investigate the chromatographic fingerprints of Radix Salviae Miltiorrhizae (RSM), its intermediate and INJECTION by HPLC-UV-MS. Methods Separation was performed on an Alltima C 18 analytical column with the mobile phase consisting of methanol-water-acetic acid as gradient eluent at the flow rate of 1 mL/min. The UV detection was set at 281 nm and TIC was recorded by an electrospray ionization mass spectrometer in negative ion mode. Results The HPLC-UV and HPLC-MS fingerprints of RSM, its intermediate and INJECTION were obtained with perfect isolation. Conclusion The fingerprints could be used for the control of RSM, its intermediate and INJECTION.