Analytical method development of methylisothiazolinone, a preservative, in rat plasma using LC-MS/MS

Abstract

Methylisothiazolinone (MI) is a preservative used in consumer products to control bacterial and fungal growth. MI can be toxic, act as a skin sensitizer and irritant, and initiate lung diseases; therefore, it is important to understand the mechanisms underlying the toxicity of MI in the body. In this study, we developed a method to analyze plasma MI by using an LC-MS/MS-coupled multiple reaction monitoring (MRM) technique, which follows the fragments of a target metabolite in rat plasma. The MRM transition of MI was m/z 116 ➔ 101, and the lower limit of quantification (LLOQ) was set at 10 ng/mL. Including the concentration of LLOQ, a seven-point calibration curve explained much of the variation in the response, and it was strongly linear (R2 = 0.9998); its intra- and inter-day accuracy and precision values were within 15% of the standard deviation (SD%) and along with the FDA and Korea Ministry of Food and Drug Safety guidelines. For intravenous (iv) pharmacokinetic studies of MI using rats, we developed an analytical method that was useful in detecting the profile of MI in the plasma. We also determined half-life, and area under the curve (AUC) of MI using a non-compartment model, and these might be useful for the study of toxic mechanisms of MI in the body.