Colorimetric detection and spectrophotometric determination of the aminothiazolyl-alkoxyimino .BETA.-lactams.

Abstract

The 2-aminothiazol-4-yl-2-alkoxyiminoacetamido substituent-containing i3-lactam antibiotics (cephalosporins and monobactams) develop a stable, concentration-dependent purple or cherry-red color after reaction with sodium nitrite in acidic condition. The color-formation is highly specific; it requires certain defined structural features such as the simultaneous presence of the intact aminothiazole-ring and an alkoxyimino substituent in the syn configuration. Other substituents on the (3-lactam nucleus have effect only on the intensity of the color. This simple and fast colorimetric procedure was found to be useful not only for the detection of this class of (3-lactam antibiotics but also for their quantitative spectrophotometric determination (2me .g 500 nm). A linear relationship exists between the intensity of the color plotted on a logarithmic scale and the concentration (12.5-200 i g/ml) of the compounds on an arithmetic scale. The j3-lactams studied in this class with definitely positive purple-red color reaction are; cefotaxime, ceftizoxime, ceftazidime, ceftriaxone, cefmenoxime, cefodizime, ceftiolene, cefpirome, aztreonam, HR 109, FK 027 (cefixime), FR 19346, SK&F 88070, FR 13300, carumonam, YM 13115, BMY 28142, DN 9550, deacetylcefotaxime, deacetoxycefotaxime and deacetylcefotaxime lactone.Most of the new semisynthetic cephalosporins and the monobactam, aztreonam, belong to the class of compounds containing the 2-aminothiazoleacetamido group. Those which contain a 2-alkoxyimino substituent at the syn-configuration are of considerable therapeutic interest. They have broad antibacterial spectra, high levels of activity especially against Gram-negative bacteria and excellent (3-lactamase stability1). These antibiotics are currently assayed using biological methods.A simple colorimetric procedure was developed based on the structural similarity between these 43-lactams and the sulfonamides, procaine (novocain) and other p-aminobenzoic acid derivatives. It was reasoned that the aromatic amino group of the aminothiazole ring of the (3-lactams similar to that of the sulfanilamides and procaine should form a colored compound after diazotization with sodium nitrite followed by coupling with N-1-naphthylethylenediamine.However, when this reaction was carried out as described in the literature2-7), there was apparently no coupling reaction, as evidenced by the lack of characteristic color. A concentration-dependent purple color did develop, however, when the sodium nitrite-treated solutions of the alkoxyiminoaminothiazolyl cephalosporins were acidified. This observation served as a basis for the development of the colorimetric detection and the spectrophotometric determination of these ,8-lactam antibiotics, as described herewith. Part of these data were previously reported8). Materials and Methods Antibiotics and Other CompoundsThe aminothiazolyl 19-lactam antibiotics and the aminothiazole-containing non-antibiotic control

Cefepime

“…These traits are responsible for the drug's greater resistance to enzyme hydrolysis and its expanded spectrum of activity, including pathogens such as strains of P aeruginosa and E. cloacae that may be resistant to other parenteral cephalosporins. The pharmacokinetic profile of cefepime supports dosing every [8][9][10][11][12] hours, consistent with most comparable antibiotic choices. The adverse reactions associated with agent are similar to those for other cephalosporins.…”

“…Cefepime is a broad-spectrum antibiotic with demonstrated in vitro bactericidal activity against large numbers of gram-negative and gram-positive clinical Based on early in vitro data,27 a minimum inhibitory concentration (MIC) of 8 As with other newer cephalosporins, the in vitro activity of cefepime is not influenced by plactamase production in staphylococci, N. The drug's activity against Enterobacteriaceae that do not express inducible p-lactamases appears comparable to that of cefotaxime and ceftazidime. In particular, cefepime may demonstrate significant activity against Citrobacter freundii, Enterobacter sp, and P aeruginosa isolates that are resistant to thirdgeneration cephalosporins.…”

“…Of the evaluable patients with LRTI in one comparative trial, 25 received cefepime 2 g every 12 hours, and 23 received ceftazidime 2 g every 8 hours. 62 The rates of satisfactory clinical response were 84% and 87%, respectively.…”

Voltammetric determination of ceftriaxon in pharmaceuticals

“…Зокрема, за спектрофотометричного аналізу в УФ-ділянці спектра цефтріаксон визначають за наявності продуктів його лужного гідролізу за електронним спектром світлопоглинання в діапазоні 230265 нм [2] чи в середовищі фосфатного буферного розчину за рН 7,4 при max= 340 та 360 нм [3]. В основі спектрофотометричних методик визначення цефтріаксону у видимій ділянці спектра лежать такі реакції [2]: комплексоутворення з іонами металів; комплексоутворення з перенесенням заряду; азосполучення з фенольними сполуками [4,5]; редокс реакції; гідроліз та наступна взаємодія із забарвленими реагентами; утворення іонних асоціатів. Для визначення залишків цефтріаксону у біологічних тканинах та фізіологічних рідинах найчастіше використовують високоефективну рідинну хроматографію з масспектрометричним детектуванням [6].…”

“…Реакцію азосполучення ще не застосовували у вольтамперометрії цефтріаксону, однак успішно використовували для спектрофотометричного визначення антибіотиків цього ряду [4,5]. Наше дослідження полягало у вивченні електрохімічної поведінки сполуки, утвореної внаслідок азосполучення цефтріаксону та його діазосолі.…”