Introduction:
Resistance to antibiotics is an ongoing concern of the pharmaceutical industry. The limited number of antibiotics in the market to treat Gram negative bacteria made their resistance an issue that is being addressed worldwide. The isolation of colistin from Bacillus polymyxa var. colistinus in Japan in 1949 and the introduction of colistin into the market in 1959 as its inactive prodrug colistin methanesulfonate (CMS) were significant milestones in the treatment of this type of infections. However, the use of colistin was decreased because of the reported nephrotoxicity and neurotoxicity associated with it. Colistin –which is a polymyxin (polymyxin E)- is currently used as a last line treatment for Multi drug Resistant (MDR) bacteria …show more content…
Proper dosage regimens are necessary since colistin is used as a last-line treatment option for resistant gram negative bacterial infections and suboptimal doses have been linked to the development of resistance. In addition to that, the nephrotoxicity and neurotoxicity associated with colistin administration requires special attention to dosing this antibiotic. To gain this knowledge requires a method for measuring colistin that is simple, rapid, specific and reliable. Unfortunately, after more than 40 years of clinical use, such information is limited due to the lack of robust analytical methods
Colistin dosages must be optimized, as colistin is a last-line treatment option and suboptimal doses have been linked to the development of resistance. In addition to that, the nephrotoxicity and neurotoxicity associated with colistin administration requires special attention to dosing this antibiotic. The lack of pharmacokinetic and pharmacodynamic studies and the absence of universal harmonization of dose units have made it difficult to derive optimal dosing regimens and specific dosing guidelines for colistin. …show more content…
The LC-MS/MS system consisted of a separations module (Alliance 2695) equipped with a solvent delivery system and an autosampler thermostatically controlled at 4°C (Waters Assoc., Milford, MA, USA) in addition to a Waters Micromass Quattro micro-API triple-quadrupole tandem mass spectrometer (ii) Chromatographic conditions. Reversed-phase chromatography is going to be performed on a C18 XBridge column (5.0 μm, 150 by 2.1 mm [inner diameter]; Waters). The mobile phase will be 0.1% (vol/vol) formic acid in acetonitrile-0.1% (vol/vol) formic acid in water (20:80, vol/vol). A flow rate of 0.2 ml·min−1, and the injection volume of 20 μl will be used. (iii) MS-MS conditions. Mass spectrometer will be operated in the positive-ion mode. Ions analysis will be performed by multiple-reaction monitoring (MRM) by employing the transition of the [M + 2H]2+ precursor to the product ions for the analytes and IS. The parameters will be optimized by infusing 10-μg/ml solutions of colistin or polymyxin B into the LC-MS/MS interface by using a built-in syringe pump set at a flow rate of 10 μl·min−1 in order to achieve the best signal-to-noise (S/N) ratio for the A and B subcomponents and the IS. The optimal MS/MS setup parameters include a +3.0-kV ion spray voltage; a 600-liter·h−1 and 350°C desolvation gas (N2) flow and temperature, respectively; a 20 liter·h−1 cone gas (N2) flow; a 120°C source temperature; a 35-V cone potential for colistin and the IS; 35-V and 25-V collision
Resistance to antibiotics is an ongoing concern of the pharmaceutical industry. The limited number of antibiotics in the market to treat Gram negative bacteria made their resistance an issue that is being addressed worldwide. The isolation of colistin from Bacillus polymyxa var. colistinus in Japan in 1949 and the introduction of colistin into the market in 1959 as its inactive prodrug colistin methanesulfonate (CMS) were significant milestones in the treatment of this type of infections. However, the use of colistin was decreased because of the reported nephrotoxicity and neurotoxicity associated with it. Colistin –which is a polymyxin (polymyxin E)- is currently used as a last line treatment for Multi drug Resistant (MDR) bacteria …show more content…
Proper dosage regimens are necessary since colistin is used as a last-line treatment option for resistant gram negative bacterial infections and suboptimal doses have been linked to the development of resistance. In addition to that, the nephrotoxicity and neurotoxicity associated with colistin administration requires special attention to dosing this antibiotic. To gain this knowledge requires a method for measuring colistin that is simple, rapid, specific and reliable. Unfortunately, after more than 40 years of clinical use, such information is limited due to the lack of robust analytical methods
Colistin dosages must be optimized, as colistin is a last-line treatment option and suboptimal doses have been linked to the development of resistance. In addition to that, the nephrotoxicity and neurotoxicity associated with colistin administration requires special attention to dosing this antibiotic. The lack of pharmacokinetic and pharmacodynamic studies and the absence of universal harmonization of dose units have made it difficult to derive optimal dosing regimens and specific dosing guidelines for colistin. …show more content…
The LC-MS/MS system consisted of a separations module (Alliance 2695) equipped with a solvent delivery system and an autosampler thermostatically controlled at 4°C (Waters Assoc., Milford, MA, USA) in addition to a Waters Micromass Quattro micro-API triple-quadrupole tandem mass spectrometer (ii) Chromatographic conditions. Reversed-phase chromatography is going to be performed on a C18 XBridge column (5.0 μm, 150 by 2.1 mm [inner diameter]; Waters). The mobile phase will be 0.1% (vol/vol) formic acid in acetonitrile-0.1% (vol/vol) formic acid in water (20:80, vol/vol). A flow rate of 0.2 ml·min−1, and the injection volume of 20 μl will be used. (iii) MS-MS conditions. Mass spectrometer will be operated in the positive-ion mode. Ions analysis will be performed by multiple-reaction monitoring (MRM) by employing the transition of the [M + 2H]2+ precursor to the product ions for the analytes and IS. The parameters will be optimized by infusing 10-μg/ml solutions of colistin or polymyxin B into the LC-MS/MS interface by using a built-in syringe pump set at a flow rate of 10 μl·min−1 in order to achieve the best signal-to-noise (S/N) ratio for the A and B subcomponents and the IS. The optimal MS/MS setup parameters include a +3.0-kV ion spray voltage; a 600-liter·h−1 and 350°C desolvation gas (N2) flow and temperature, respectively; a 20 liter·h−1 cone gas (N2) flow; a 120°C source temperature; a 35-V cone potential for colistin and the IS; 35-V and 25-V collision