- Cefuroxime axetil-3-ene isomer preparation method
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The invention relates to a cefuroxime axetil-3-ene isomer preparation method, and belongs to medicine quality research, quality control and safety research of pharmaceutical enterprises. The steps comprise: (1) in an aprotic solvent and a protic solution, generating a 3-ene isomeric cefuroxime axetil and cefuroxime axetil mixture from cefuroxime axetil under the catalytic action of an alkali; and(2) purifying the 3-ene isomeric cefuroxime axetil and cefuroxime axetil mixture obtained in the step (1) through reversed-phase C18 column preparative liquid chromatography, extracting, drying, andconcentrating to obtain the cefuroxime axetil-3-ene isomer, wherein the chromatographic conditions of purifying comprise that a ratio of water to methanol is 40/60, the flow rate is 40 ml/min, and theultraviolet detection wavelength is 23 nm. According to the invention, the method has advantages of simple reaction operation, mild conditions and high product purity, and the obtained cefuroxime axetil-3-ene isomer can be used as a standard substance in quality control of cefuroxime axetil bulk drugs and preparations.
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Paragraph 0019-0034
(2020/01/03)
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- Stability of cephalosporin prodrug esters in human intestinal juice: Implications for oral bioavailability
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The levels of degradation of cefetamet pivoxil (CAT), cefuroxime axetil (CAE), and cefpodoxime proxetil (CPD) in 0.6 M phosphate buffer (pH 7.4) and human intestinal juice (pH 7.4) at 37°C over 24 h were compared. Significant differences in the time courses of degradation and in the patterns of degradation products were observed. (i) The relative proportions of the Δ2- and Δ3-cephalosporins were roughly reversed in the two incubation media. In phosphate buffer, the major degradation product was the Δ2-cephalosporin (CAT = 61%; CAE = 74%; CPD = 85%), while in intestinal juice it was the Δ3- cephalosporin (CAT = 86%; CAE = 75%; CPD = 87%). (ii) Generally, the degradation of the prodrug esters progressed faster in intestinal juice than in phosphate buffer (e.g., for CAT the half-lives [t(1/2)s] were 0.78 and 4.3 h, respectively). (iii) The two diastereoisomers of CAE and CPD were degraded at different rates in intestinal juice (for the CAE diastereoisomers, t(1/2)s = 0.37 and 0.93 h; for the CPD diastereoisomers, t(1/2)s = 0.18 and 0.98 h) but were degraded at similar rates in phosphate buffer (for the CAE diastereoisomers, t(1/2) = 1.6 h; for the CPD t(1/2) diastereoisomers, = 2.2 h). It is concluded that (i) the Δ2 isomerization does not significantly affect the bioavailability of prodrug esters since enzymatic hydrolysis in the intestinal fluid proceeds mainly to the active Δ3-cephalosporin and (ii) the high degree of stereoselectivity of the enzymatic ester hydrolysis should make it possible to increase the bioavailabilities of certain prodrug esters (CAE, CPD) by using the more stable diasterioisomer.
- Stoeckel, Klaus,Hofheinz, Werner,Laneury, Jean Paul,Duchene, Patrick,Shedlofsky, Steve,Blouin, Robert A.
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p. 2602 - 2606
(2007/10/03)
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