Measurement of lidocaine and 2,6-dimethylaniline in minipig plasma, skin, and dermal tapes using UHPLC with electrospray MS/MS

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2018-06, Vol.1087-1088, p.158-172
• Main Authors: Li, Qian, Magers, Tobias, King, Brad, Engel, Brian J., Bakhtiar, Ray, Green, Charisse, Shoup, Ronald
• Format: Article
• Language: English
• Subjects: 2,6-Dimethylaniline; 2,6-Xylidine; 4-Methoxybenzoyl chloride; Adhesives; Administration, Cutaneous; Aniline Compounds - administration & dosage; Aniline Compounds - analysis; Aniline Compounds - blood; Aniline Compounds - pharmacokinetics; Animals; Chromatography, High Pressure Liquid - methods; Female; Lidocaine; Lidocaine - administration & dosage; Lidocaine - analysis; Lidocaine - blood; Lidocaine - pharmacokinetics; Linear Models; Minipig; Reproducibility of Results; Sensitivity and Specificity; Skin; Skin - chemistry; Skin - metabolism; Swine; Tandem Mass Spectrometry - methods; Tape stripping
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2018.04.030

Sensitive LC-MS/MS methods were developed to measure lidocaine and its metabolite 2,6-dimethylaniline (2,6-DMA) with application to transdermal studies. The methods for lidocaine in minipig plasma, tissue biopsies, and dermal tapes utilized mixed mode/SCX solid phase extraction, with lower quantitation limits of 25 pg/mL in plasma, 15 ng/g tissue, and 5 ng/tape. 2,6-DMA was measured in plasma and skin tissue homogenates by ultrafiltration and (for tissue) by further derivatization with 4-methoxybenzoyl chloride to form the corresponding benzamide derivative, which extended the lower limit of quantitation to 200 pg/mL. The methods allowed local measurement of lidocaine in stratum corneum, punch biopsies, and plasma and of 2,6-DMA in plasma and biopsies obtained from minipigs dosed with experimental transdermal formulations. Quantitation limits were approximately 7-fold lower than previously reported for lidocaine and 3-fold lower for 2,6-DMA.