Simultaneous Microdetermination of Different Penicillin Antibiotics Residues for Cross Contamination Study in Non-Penicillin Dosage Forms

Abstract

Cross-contamination of pharmaceutical dosage forms is an attentive problem constituting obstacle towards prosperous therapeutic goals. Cross-contamination of non-penicillin products with penicillin drugs can initiate life-threatening allergic hypersensitivity reactions, thus, all non-penicillin products should be tested for contamination before sale. This work presents a rapid HPLC-DAD method for the simultaneous determination of nine penicillin drugs for studying cross contamination of non-penicillin pharmaceutical dosage forms as syrups, respiratory solution, creams, tablets, inhaler capsules and capsules. Chromatographic separations were performed on a reversed phase atlantis -C18 (150 x 4.6 mm) column using gradient elution with a mobile phase containing 0.02M sodium phosphate buffer and methanol and diode array detector set at 220 nm. The optimized chromatographic conditions allowed separation of the nine penicillins from non-penicillin drugs and their co-formulated excipients with good chromatographic parameters and high purity profiles. Validation of the method was performed as per ICH guidelines where low limits of detection (0.1-1 µg. mL-1) were obtained for all the studied compounds indicating good sensitivity. The proposed method was applied successfully for studying cross contamination of different non-penicillin products including salbutamol syrup and respiratory solution, miconazole cream, biperiden tablet, formoterol inhaler capsule and omeprazole capsule with residues of 9 penicillin drugs. Hence, the proposed method can be recommended for the routine quality control to study and determine cross contamination of the non-penicillin facility with trace amounts of any of the studied penicillins with high accuracy and precision.

Keywords: Cross contamination, penicillin residues, non-penicillin products, HPLC-DAD, validation