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Quantification of Vancomycin and Clindamycin in Synovial Tissue and Bone Using Ultra-High-Performance Liquid
Amanda J Holst1, Soma Bahmany1, Angela C J van Dorp1
1Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Background:
Approximately 1-2% of patients undergoing hip or knee arthroplasty encounter a periprosthetic joint infection (PJI). Currently, the treatment involves revision surgeries and long-term antibiotic therapy. However, too low antibiotic concentrations can lead to treatment failure, whereas excessively high concentrations can lead to adverse events. Although optimal dosing is very important, there remains an insufficient understanding of the relationship between the concentrations of the plasma and antibiotics at the target site. This study aimed to develop and validate a novel ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique for quantifying two frequently prescribed antibiotics, vancomycin and clindamycin, in synovial tissue and bone samples.
Methods:
Method validation was performed based on the guidelines of the European Medicines Agency (EMA) and US Food and Drug Administration (FDA).
Results:
The method was found linear for vancomycin from 0.8 to 25 μg/g and for clindamycin from 0.5 to 25 μg/g in the bone and from 1 to 25 μg/g for both compounds in synovial tissue ( r2 > 0.990). The results of the validation of precision, accuracy, and carry-over were all within the acceptable ranges. All clindamycin extracts were stable in the autosampler for the bone and synovial tissue samples for up to 24 hours. Vancomycin extracts were stable in synovial tissue for up to 24 hours but not in bone sample extracts.
Conclusions:
A method for quantifying vancomycin and clindamycin in synovial tissue and bone using UHPLC-MS/MS was developed and validated.
Insights
A new method accurately measures vancomycin and clindamycin in bone and joint tissues after surgery. This aids in optimizing antibiotic dosing for periprosthetic joint infections (PJIs).
Area of Science:
- Analytical Chemistry
- Pharmacokinetics
- Orthopedic Surgery
Background:
- Periprosthetic joint infections (PJIs) affect 1-2% of patients undergoing hip or knee arthroplasty.
- Current PJI treatment relies on revision surgery and prolonged antibiotic therapy.
- Suboptimal antibiotic concentrations at the infection site can lead to treatment failure or adverse events.
Purpose of the Study:
- To develop and validate a novel ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method.
- To quantify vancomycin and clindamycin concentrations in synovial tissue and bone samples.
- To improve understanding of antibiotic pharmacokinetics in PJI treatment.
Main Methods:
- Development of a UHPLC-MS/MS technique for antibiotic quantification.
- Method validation adhering to European Medicines Agency (EMA) and US Food and Drug Administration (FDA) guidelines.
- Testing linearity, precision, accuracy, carry-over, and stability of antibiotic extracts.
Main Results:
- The UHPLC-MS/MS method demonstrated excellent linearity for vancomycin and clindamycin in bone and synovial tissue (r2 > 0.990).
- Validation parameters for precision, accuracy, and carry-over were within acceptable limits.
- Clindamycin extracts were stable for 24 hours; vancomycin extracts were stable in synovial tissue but not bone.
Conclusions:
- A validated UHPLC-MS/MS method for quantifying vancomycin and clindamycin in synovial tissue and bone has been successfully developed.
- This method provides a crucial tool for pharmacokinetic studies in PJI.
- Optimized antibiotic dosing strategies can be informed by these tissue concentration measurements.
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