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Updated: Dec 10, 2025
Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Application of an LC-ESI-QTOF-MS method for evaluating clindamycin concentrations in plasma and prostate
Lisiani Ritter1, Eduarda Possa2, Larissa Bergoza2
1Institute of Biotechnology, University of Caxias do Sul, Caxias do Sul, Brazil.
Abstract:
Clindamycin is used for infections caused by Gram-positive and Gram-negative anaerobic pathogens and Gram-positive aerobes. Propionibacterium acnes is an important opportunistic microorganism of the human skin and is related to prostatitis. An LC-electrospray ionization-quadrupole time-of-flight-MS method was validated for determining clindamycin concentrations in plasma and prostate microdialysate. Clindamycin separation was carried out on a C18 column at 0.5 mL/min. The mobile phase employed gradient elution of formic acid and methanol. A mass spectrometer was operated in positive electrospray ionization mode to monitor ion 425.1784 and 253.1152 for clindamycin and cimetidine (internal standard), respectively. Linearity was obtained at 0.5-10.0 μg/mL (plasma) and 0.05-1.0 μg/mL (microdialysate) with coefficients of determination ≥0.999. The intra- and inter-day precision (coefficient of variation - CV%) values were ≤13.83% and 12.51% for plasma, respectively, and ≤10.90% and 9.35% for microdialysate, respectively. The accuracy was between 90.82% and 108.25% for plasma, and 96.97% and 106.98% for microdialysate. The present method was fully validated and applied to investigate clindamycin concentrations in both plasma and prostate by microdialysis in Wistar rats (80 mg/kg, intravenous). Because the penetration of antibiotics into the prostate may be restricted, this method allows us to investigate the prostate concentrations of clindamycin for the first time.
Insights
A new method accurately measures clindamycin in plasma and prostate tissue. This allows researchers to study antibiotic penetration into the prostate, crucial for treating infections like prostatitis.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Analytical Chemistry
- Infectious Diseases
Background:
- Clindamycin treats infections from Gram-positive and Gram-negative anaerobic bacteria.
- Propionibacterium acnes, linked to prostatitis, is a relevant pathogen.
- Antibiotic penetration into the prostate can be limited, necessitating accurate measurement methods.
Purpose of the Study:
- To develop and validate a liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry (LC-ESI-QTOF-MS) method.
- To quantify clindamycin concentrations in both plasma and prostate microdialysate.
- To enable the first investigation of clindamycin concentrations within the prostate.
Main Methods:
- Validated an LC-ESI-QTOF-MS method using a C18 column and a gradient elution of formic acid and methanol.
- Monitored specific ions for clindamycin and cimetidine (internal standard) in positive electrospray ionization mode.
- Applied the validated method to Wistar rats receiving an intravenous dose of clindamycin (80 mg/kg).
Main Results:
- The method demonstrated excellent linearity (R² ≥ 0.999) across specified ranges for plasma and microdialysate.
- High accuracy (90.82–108.25% for plasma, 96.97–106.98% for microdialysate) and acceptable precision (CV% ≤ 13.83% for plasma, ≤ 10.90% for microdialysate) were achieved.
- The validated method was successfully used to measure clindamycin levels in rat plasma and prostate tissue via microdialysis.
Conclusions:
- A robust and validated LC-ESI-QTOF-MS method for clindamycin quantification in plasma and prostate microdialysate has been established.
- This analytical method provides a crucial tool for pharmacokinetic studies, particularly for assessing antibiotic distribution in the prostate.
- The findings pave the way for better understanding and optimizing clindamycin treatment for prostate infections.
