( D Garteiz TexMS Analytical S...)Quantitation of Oxybutynin in Rabbit Plasma Using the Varian 1200L LC/MS/MS System

D Garteiz, TexMS Analytical Services, Houston, TX

Introduction

A Varian 1200L LC/MS/MS system was used for the quantitation of the plasma levels oxybutynin obtained by topical delivery of therapeutic agents to the urinary tract using a urethra suppository mode of administration.

Background Urinary tract disease is a major health problem in the U.S. and will continue to grow with an increasingly aging population. Urinary incontinence accounts for over ten million patients suffering from urinary tract disease in the United States. Although oral delivery of drugs is an effective method of treating incontinence, many patients are unable to continue oral drug therapy because of severe side effects such as dry mouth, nausea, and tachycardia. One method of satisfying the clinical need of treating patients refractory to oral medication is through topical delivery of therapeutic agents to the urinary tract. The urethra provides an accessible and potentially effective method for achieving topical drug delivery to the urinary tract and surrounding organs and tissues.

One of the most commonly used drugs for urinary tract disease is oxybutynin chloride (Figure 1). Because of the severity of the drugs side effects, low doses are administered, leading to oxybutynin plasma levels that can range from the low pg/mL to low ng/mL. The present study investigates the feasibility of providing therapeutic agents to the urinary tract by absorption through the urethra.

Using a rabbit model, urethral suppositories, formulated with oxybutynin chloride were placed in the urethra of female rabbits. The suppositories liquefy in the urethra and transfer the oxybutynin through the urethral mucosal into the systemic circulation. Safety of urethral absorption of oxybutynin was established by comparing the plasma levels of urethral absorption of oxybutynin versus levels achieved by
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