Method validation for identification and determination of Methylisothiazolinone and Chloromethylisothiazolinone in cosmetics by LC-MS/MS QTOF

Yustina Yustina; Nenden Solihatul Zannah; Sri Purwaningsih; Endang Lukitaningsih

doi:10.22146/ijp.16886

Yustina Yustina National Quality Control Laboratory of Drug and Food, Indonesian FDA
Nenden Solihatul Zannah National Quality Control Laboratory of Drug and Food, Indonesian FDA
Sri Purwaningsih National Quality Control Laboratory of Drug and Food, Indonesian FDA
Endang Lukitaningsih Faculty of Pharmacy, Universitas Gadjah Mada

Keywords: Cosmetic products, Chloromethylisothiazolinone, methylisothiazolinone, LC-MS/MS QTOF, Preservatives

Abstract

Broad-spectrum preservatives known as isothiazolinone biocides are frequently found in cosmetic, industrial, and household products. Certain isothiazolinones (methylisothiazolinone, MIT, and chloromethylisothiazolinone, CMIT) might result in eczema, edema, or allergic contact dermatitis by dermal contact or inhalation. This study aims to develop and validate the identification and determination method of a single MIT and MIT/CMIT mixture utilizing UPLC fitted with tandem mass spectrometry quadrupole time of flight (QTOF) for various beauty products.

Several evaluations, including specificity, linearity, recovery, stability, precision, accuracy, determination of detection limit (LOD), and quantitation limit (LOQ) were conducted after some optimization processes by using LC-MS/MS QTOF. The MRM transition ion of MIT was m/z 116.0165 → 99.0091, 101.0215, and 84.9954. Meanwhile for CMIT was m/z 149.9775 → 134.9977, 86.9906, and 115.0447. MIT and CMIT were successfully distinguished and identified. The retention times of MIT and MCIT were detected at 4.53, and 5.25 min, respectively. Good selectivity was achieved by using the approach with resolution value greater than 1.5. The linearity range for single MIT was 375-1125 ng/mL, meanwhile for MIT/CMIT mixture resulted in 107.68-323.04 ng/mL for MIT and 295.36-886.08 for CMIT, respectively. Furthermore, the calibration curve approach was used to determine LOD acquired. In addition, LOQ over the LOD value was 0.00003%. These findings proved the suitability of the developed method to quantify MIT and CMIT in cosmetics. Samples of 21 cosmetic products, including soaps, shampoos, lotions, lipstick, and liquid cosmetics, from local markets and pharmacies were analysed using the developed method. Three of them were found to contain both single MIT or MIT/CMIT mixture. The technique and the data will help the Indonesian FDA to regulate the compounds used in cosmetics.

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