Liquid Chromatographic Method for the Simultaneous Determination of Imipenem and Sulbactam in Mouse Plasma

Abstract

The first analytical method is developed and validated for the simultaneous determination of imipenem and sulbactam in mouse plasma. Sample treatment is based on plasma stabilization with 4-(2-hydroxyethyl)piperazine-ethanesulfonic acid (HEPES) (0.5 mol/L; pH 7.0)-water-ethylene glycol (2:1:1, v/v/v), precipitation of plasma proteins with acetonitrile, centrifugation, evaporation, and reconstitution with borate buffer. Analytical determination is carried out by high-performance liquid chromatography with diode-array detection. Chromatographic separation is achieved within 11 min on a C(18) column by gradient elution with borate buffer (0.1 mol/L, pH 7.2) and methanol. Imipenem and sulbactam are monitored at 295 and 230 nm, respectively. The overall interday accuracy is in the range of 95% to 100% and from 98% and 101% for imipenem and sulbactam, respectively. Interday precision is below 8% and 4% for imipenem and sulbactam, respectively. Limits of quantitation of imipenem and sulbactam are 0.05 and 1.0 microg/mL, respectively. The mean extraction recoveries are 94.5% and 94.2% for imipenem and sulbactam, respectively. The described method allows an accurate, simple, and rapid identification and quantitation of imipenem and sulbactam in mouse plasma. This method is applied to the analysis of imipenem and sulbactam in mouse plasma after drug administration.

A liquid chromatography assay for a quantification of doripenem, ertapenem, imipenem, meropenem concentrations in human plasma: Application to a clinical pharmacokinetic study

“…Various chromatographic methods with UV detection were developed to measure total plasma concentrations of carbapemens in plasma . These assays concern mainly imipenem [5][6][7][8][9]21], meropenem [10,12,[14][15][16][17][18][19]21] and ertapenem [11,[21][22][23][24][25]. Two assays based on ultrafiltration [20] and solid phase extraction [13] were only reported for doripenem.…”

Hydrophilic interaction chromatography/tandem mass spectrometry for the simultaneous determination of three polar non‐structurally related compounds, imipenem, cilastatin and an investigational β‐lactamase inhibitor, MK‐4698, in biological matrices

“…IMP, CIL and BLI are highly polar analytes. Most of the previously published HPLC methods for IMP and CIL were performed on C8 or C18 reversed‐phase (RP) material using mobile phases containing borate or phosphate buffers 7–12. Even at as low as 10% acetonitrile or methanol in the mobile phase, no sufficient retention was observed, especially for IMP.…”

“…The historical methods to analyze Primaxin® were reported as separate assays for the two analytes, IMP and CIL, respectively. For imipenem, several methods that have been reported were based on either microbiological assays,6, 7 which cannot differentiate imipenem from other coadministered antibiotics, or high‐performance liquid chromatography (HPLC) with ultraviolet (UV) detection after either ultrafiltration8, 9 using relatively large volume of samples, or, most recently, protein precipitation10, 11 with limited dynamic ranges (≤100‐fold). For cilastatin, HPLC methods that involved solid‐phase extraction using C18 cartridges, and then reversed‐phase chromatography followed by either post‐column derivatization for fluorescence detection,12 or direct UV detection,13 have been described in determination of the analyte in biological fluid.…”

Simultaneous analysis of amoxicillin and sulbactam in human plasma by HPLC-DAD for assessment of bioequivalence

“…Therefore, a suitable method for simultaneous determination of these drugs is required. Many HPLC methods are available for the measurement of amoxicillin [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] or sulbactam [22][23][24][25][26][27] in biological samples, individually [6][7][8][9][10][11][12] or in combination with other drugs or metabolites [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. In past, the plasma concentrations of amoxicillin and sulbactam are mainly measured via HPLC-UV or HPLC-mass spectrometry.…”