• 분석과학
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• 제32권4호
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• pp.147-154
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• 2019

Ampicillin and Sulbactam (2:1, w/w) are combined in formulation to provide broader antibacterial action in treatment of many infections. The development of analytical method for simultaneouly determine these two compounds was difficult because of the differences in their chemical structures and ratio in the formulation. Current published methods still have some limitations. In this study, we developed an alternative high-performance liquid chromatography (HPLC) assay method for simultaneously determination of ampicillin sodium and sulbactam sodium in powder for injection. Method validation of HPLC method was conducted to determine linearity, precision, accuracy, system suitability, robustness. The linearity of the calibration curves in the desired concentration range was good ($r^2$> 0.9994). RSDs of intra-day and inter-day precision obtained were less than 2.00 %. Accuracy was obtained with the recoveries in range of 98.42 % and 101.36 %. As a result of system suitability, RSD of both retention time and the peak area obtained were not more than 1.0 %. The values of plate number were more than 7000 and symmetric factors obtained were 0.8. As intermediate-precision and robustness of the developed assay, it could be expected to become valuable tools for revising the Korean Pharmacopoeia (KP XI).

• 약학회지
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• 제41권1호
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• pp.126-131
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• 1997

To overcome the problems of the resistance to clavulanic acid, many researchers are developing novel inhibitors that are not sensitive to new mutant ${\beta}$-lactamases. In order to evaluate newly synthesized compound CH2150 (Sodium (3S.5R)-6(Z)-[1-{1-(2-{2-benzoxazoly}thioethyl)-l.2,3-txiazol-4-yl}methylene] penicillanate-1,1-dioxide) as a ${\beta}$-lactamase inhibitor, we examined inhibitory activity of CH2150 against ${\beta}$-lactamases of clinical isolates resistant to ampicillin/sulbactam(12 strains of Escherichia coli and 13 strains of Staphylococcus aureus), and compared with that of sulbactam. Nitrocefin was used as substrate for ${\beta}$-lactamases, and the increase of absorbance was measured spectrophotometerically at 482 nm. ${\beta}$-Lactarnase inhibition of CH2150 against ${\beta}$-lactamases was 73 ~ 96% in E. coli and 76 ~ 79% in S. aureus. Comparatively, that of sulbactam was 96 ~ 100% and 96 ~ 100%, respectively. The inhibitory activity of CH2150 was slightly lower than that of sulbactam. The MIC values of ampicillin combined with CH2150 (2:1) for the clinical isolates were 4~512 ${\mu}$g/ml for E. coli and 1.0 ~ 64 ${\mu}$g/ml for S. aureus, whereas 0.5~16 ${\mu}$g/ml for E. coli and 0.25~8 ${\mu}$g/ml for S. aureus when combined with sulbactam (2:1).

• 약학회지
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• 제46권6호
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• pp.381-386
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• 2002

The synthesis of new 6-exomethylene sulbactam derivatives with 5-methyl-1,3,4-thiadiazole was described. The 6,6-dibromopenam 5 was reacted with $CH_3$MgBr and carbaldehyde 4 to afford the 6-bromo-6-(1-hydroxy-1-methyl)penicillanate 6, which was treated with acetic anhydride to give acetoxy compound 7. The deacetobromination of acetoxy compound 7 with zinc and acetic acid gave 6-exomethylen penams, Z-isomer 8 and E-isomer 9, which was oxidized to sulfones 10 by m-CPBA. The p-methoxybenzyl compounds 6-10 were deprotected by AlCl$_3$ and neutralized with NaOH solution to give the sodium salts 11-15.

• 한국임상약학회지
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• 제14권2호
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• pp.96-99
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• 2004

Aminophylline, ceftriaxone 및 ampicillin/sulbactam (Unasyn)을 미숙아용 고영양수액제에 직접 첨가하거나 Y-site로 투여하는 경우의 안정성에 관해 조사하였다. Aminophylline 주사액 (25mg/mL) $300{\mu}l$와 ceftriaxone sodium (37.5 mg/mL) 2mL를 각각 고영양수액제 직접 첨가하였다. 또한 Y-site에서의 안정성 조사를 위해 ceftriaxone sodium (37.5 mg/mL)을 고영양수액제에 각각 1:1 및 1:2 부피비가 되도록 혼합하였고 Unasyn (25mg/mL)은 고영양수액제와 1:1의 부피비로 혼합하였다. 이상과 같이 조제한 혼합액을 $25^{\circ}C$와 $4^{\circ}C$에 보관하여 aminophylline은 48시간 동안 그리고 항생제들은 24시간 동안의 경시변화를 HPLC를 이용하여 분석하였다. Aminophylline은 위 보존조건에서 48시간동안 안정하였다(변화율 <$10{\%}$). Ceftriaxone sodium을 고영양수액제에 직접 첨가한 경우 ceftriaxone의 잔존률은 $25^{\circ}C$에서 4시간째에 $90.5{\pm}1.8{\%}$이었고 $4^{\circ}C$에는 $95.1{\pm}1.4{\%}$로 측정되었다. Y-site에서의 안정성과 관련하여 ceftriaxone sodium을 고영양수액제와 1:1로 혼합한 경우 양 보존조건에서 ceftriaxone은 24시간 동안 안정하였으나 1:2로 혼합한 경우에는 $4^{\circ}C$ 보관 시에만 안정하였고 $25^{\circ}C$에서는 24시간째에 약 $14{\%}$ 정도 분해되는 것으로 나타났다. 한편, Unasyn의 경우 ampicillin은 24시간째에 $4^{\circ}C$ 보관 시에만 안정하였고 $25^{\circ}C$에서는 24시간째에 약 $14{\%}$정도 분해되는 것으로 나타났다. 한편, Unasyn의 경우 ampicillin은 24시간째에 $4^{\circ}C$에서는 안정하였으나 $25^{\circ}C$에서는 $30{\%}$까지 감소되는 것으로 분석되었고 sulbactam은 24시간째에 온도와 관계없이 안정한 것으로 나타났다. Ceftriaxone sodium을 TPN과 Y-site 혼합 후 1-2시간 이내에 침천이 형성되었고 Unasyn의 경우에는 12시간째에 침천이 형성되었다. 혼합액의 pH나 색상은 연구기간 동안 일정하였다. 이러한 연구결과에 기초할 때, aminophylline은 고영양수액제와 혼합가능하고 ceftriaxone과 Unasyn은 고양양수액제와 혼합시 최소 1시간 동안은 안정한 것으로 평가되었다.

• 약학회지
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• 제43권6호
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• pp.782-788
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• 1999

7-Oxocephalosporanate 1 was treated with phosphonium salts 2~4 by Wittig reaction to afford 7-exomethylene cephalosporanates 5~7. They were oxidized to sulfones 8~10 with mCPBA. Deprotecton of benzhydryl 7-exomethylene cephalosporanate with $AlCl_3$ and NaHCO_3$ gave sodium salts of 7-exomethylene cephalosporanates 11~16. The ${\beta}-lactamase$ inhibitory activity of synthesized compounds 11~16 were compared with sulbactam, tazobactam and clavulanic acid against Type I, II, III, IV and TEM-2 $\beta$-lactamase in vitro. Compound 15 showed more potent activity than sulbactam and clavulanic acid against Type III, IV ${\beta}-lactamase$ enzyme.

• Journal of Applied Biological Chemistry
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• 제58권3호
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• pp.227-232
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• 2015

A microarray study has been employed to understand changes of gene expression in E. coli KD43162 resistant to ampicillin, ampicillin-sulbactam, piperacillin, piperacillin-tazobactam, cefazolin, cefepime, aztreonam, imipenem, meropenem, gentamicin, tobramycin, ciprofloxacin, levofloxacin, moxifloxacin, fosfomycin, and trimethoprim-sulfamethoxazole except for amikacin using disk diffusion assay. Using Sodium dodecyl sulphate-polyacrylamide gel electrophoresis and MALDI-TOF MS analyses, 36 kDa of outer membrane proteins (OMPs) was found to be deleted in the multidrug resistant E. coli KD 43162. Microarray analysis was used to determine up- and down-regulated genes in relation to multidrug resistant E. coli KD43162. Among the up-regulated genes, these genes were corresponded to express the proteins as penicillin-binding proteins (PBPs), tartronate semialdehyde reductase, ethanolamine utilization protein, shikimate kinase I, allantoinase, predicted SAM-dependent methyltransferase, L-glutamine: D-fructose-6-phosphate aminotransferase (GFAT), phospho-glucosamine mutase, predicted N-acetylmannosamine kinase, and predicted N-acetylmannosamine-6-P epimerase. Up-regulation of PBPs, one of primary target sites of antibiotics, might be responsible for the multidrug resistance in E. coli with increasing amount of target sites. Up-regulation of GFAT enzyme may be related to the up-regulation of PBPs because GFAT produces N-acetylglucosamine, a precursor of peptidoglycans. One of GFAT inhibitors, azaserine, showed a potent inhibition on the growth of E. coli KD43162. In conclusion, up-regulation of PBPs and GFATs with the loss of 36 kDa OMP refers the multidrug resistance in E. coli KD 43162.