Development and Validation of a Sensitive and Robust Wipe‐Test Method for the Detection and Quantification of the Antibiotic Ertapenem and its Primary Degradates in a Pharmaceutical Manufacturing Environment

Abstract

A sensitive HPLC method for the detection and quantification of residual amounts of the 1β‐methyl carbapenem antibiotic ertapenem and its primary degradates in swabs collected from manufacturing equipment surfaces was developed and validated. The method utilizes a Waters YMC basic column at ambient temperature, aqueous phosphoric acid and acetonitrile as mobile phases, and UV detection at 230 nm. The method employs gradient elution. The injection precision, linearity, limit of quantitation, limit of detection, selectivity, accuracy, ruggedness, and stability of the method were evaluated and found to be satisfactory. The HPLC method was validated using a swabbing or wipe‐test procedure with 4 swabs moistened with 3‐(N‐morpholino) propane sulfonic acid buffer at pH 7. The limit of quantitation (LOQ) and limit of detection (LOD) were determined to be 0.016 µg/mL (representing 0.16 µg/wipe‐test) and 0.0006 µg/mL (representing 0.006 µg/wipe‐test), respectively. The solution stability of a 2.0 µg/mL standard solution was evaluated for 18.5 hours at 5°C and found to be satisfactory. The frozen (−20°C) swab stability revealed that the swabs were stable for up to 4 days.

Keywords:

• Pharmaceuticals
• manufacturing
• ertapenem
• antibiotics
• cleaning validation
• swab analysis
• HPLC

Acknowledgments

We gratefully acknowledge our colleagues at Merck Research Laboratories for their support in the present study.