Liquid Chromatographic Method for the Determination of Cefadroxil in its Suspension and in Serum

Abstract

We have described a simple, accurate, sensitive and reproducible reverse phase HPLC method for the measurement of cefadroxil in the commercially available suspension and in serum. The mobile phase consisted of sodium phosphate buffer and methanol and the internal standard was cefaclor. The samples were injected onto an Ultrasphere C₈ column and the detector was set at 230 nm. The standard curves were linear and the detection limit was 0.5 mcg/ml. The interday and intraday coefficient of variation was <4.7%. The method was successfully used to: 1) determine the stability of cefadroxil in the commercially available suspension; and, 2) measure serum cefadroxil concentration in a pediatric patient with osteomyelitis.

Cefadroxil is a first-generation oral cephalosporin, which is indicated for the treatment of pharyngitis and tonsillitis, skin and skin structure infections, and urinary tract infections caused by susceptible microorganisms.¹ It appears to possess an antistaphylococcal activity of oral antibiotics. It is possible that cefadroxil could be prepared for the complete course of therapy for a p3tienl and thus, avoid the need for return visits to the pharmacy. It may also be possible to reconstitute and store cefadroxil in the department of pharmacy without loss of potency. This may reduce pharmacy time spent in reconstitution for each individual cefadroxil prescription.

One patient (age 22 months, weight 10 kg) with osteomyelitis was studied after cefadroxil oral dose of 60 mg/kg every 12 hours. Blood samples (0.50 ml) were collected, just prior to the dose (0 hr), and at 1, 2, 6, and 12 hours after the dose. The peak serum concentration (Cmax) of cefadroxil in this patient was 35.4 mcg/ml at a 60 mg/kg dose, compared with a previously reported peak concentration of 11.0 ug/ml at the dose of 15 mg/kg and 7.4 mcg/ml at 10 mg/kg dose.² The peak in our patient occurred at 1 hour after the dose, as was previously reported. The lowest serum concentration (Cmin) in our patient was 0.5 mcg/ml, and it occurred at the end of 12-hour dosage interval. Thus, our HPLC method proved simple, sensitive, accurate and reproducible for (he measurement of cefadroxil in the commercially available suspension formulation, as well as in the serum of a pediatric patient. This could be used to conduct the pharmacokinetics and pharmacodynamics studies for the development of optional dosage guidelines of cefadroxil in pediatric patients.

With the recent efforts to contain health care costs, an increasing number of patients are being sent home with a supply of cefadroxil suspension. Thus, it would be of interest to evaluate its chemical stability over an extended period. However, no HPLC method has been described to measure cefadroxil in a suspension formulation.

This article describes a simple, accurate, sensitive and reproducible reverse-phase HPLC method for the determination of cefadroxil in the commercially available suspension and serum of a pediatric patient with osteomyelitis.