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Meropenem interference on phosphate measurement: utility of reaction curve analysis in automated biochemistry
Chun-Fung So1, Rachel Sze-Wan Yiu1, Tsz-Ki Ling1
1Division of Chemical Pathology, Department of Pathology, Queen Mary Hospital, Hong Kong, China.
Background:
Analytical errors in plasma phosphate measurement can result in inappropriate treatment. Meropenem, not previously known to affect plasma phosphate assays, was suspected to be the interferent after a case of negative phosphate measurement with abnormal reaction curve for a meropenem-containing specimen on the Roche Cobas 8000 Analytic System. We studied the effect of meropenem on Roche's phosphate assay and the utility of reaction curve analysis in interference detection.
Methods:
Meropenem-spiked plasma specimens with a range of estimated meropenem concentrations were prepared by mixing pooled human plasma from 46 patients and 20 mg/mL meropenem in normal saline in predetermined volume ratios. The relationship between meropenem concentration and percentage difference on apparent phosphate concentration on Roche was recorded as an interferogram. Reaction curves generated by the analyzer were also examined.
Results:
Percentage difference on apparent phosphate concentration on Roche increases with meropenem concentration, with < -100% difference (i.e. negative measured phosphate) at estimated meropenem concentrations of ≥9.3 mg/mL. The negative interference was within acceptable limits defined by the Royal College of Pathologists of Australasia at an estimated meropenem concentration of 1.3 mg/mL (>50× therapeutic levels). Reaction curves of meropenem-containing samples were markedly different from the control.
Conclusion:
Meropenem leads to negative, spectral, concentration-dependent, platform-specific interference on Roche phosphate assay. Reaction curve analysis improves interference detection in automated biochemistry analyzers and should be implemented in the form of laboratory protocols to prevent analytical errors and patient harm.
Insights
Meropenem causes analytical errors in plasma phosphate measurements, leading to falsely low results on the Roche Cobas 8000 system. Reaction curve analysis can help detect this interference.
Area of Science:
- Clinical Chemistry
- Analytical Toxicology
Background:
- Plasma phosphate measurement errors can lead to incorrect patient treatment.
- Meropenem was suspected to interfere with phosphate assays after a case of negative results.
Purpose of the Study:
- To investigate the interference of meropenem on Roche phosphate assays.
- To evaluate the use of reaction curve analysis for detecting interference.
Main Methods:
- Prepared meropenem-spiked plasma specimens at various concentrations.
- Recorded the relationship between meropenem concentration and phosphate measurement difference (interferogram).
- Examined analyzer-generated reaction curves.
Main Results:
- Meropenem caused a concentration-dependent negative interference, resulting in negative phosphate readings at high concentrations.
- Interference exceeded acceptable limits at concentrations above 50x therapeutic levels.
- Meropenem-containing samples showed distinct reaction curves compared to controls.
Conclusions:
- Meropenem induces negative, spectral, concentration-dependent interference specific to the Roche phosphate assay.
- Reaction curve analysis enhances interference detection in automated analyzers and should be integrated into lab protocols to prevent errors and patient harm.
