Determination of Lorazepam in Rabbit Plasma After Intranasal Administration by LC-MS

Abstract

An LC-MS method was developed and validated to determine lorazepam in rabbit plasma. Chromatographic separation was performed on a C18 column using methanol-150 nM sodium acetate (62.5:37.5, v/v) as the mobile phase at the flow rate of 0.2 mL min−1. The retention times for lorazepam and diazepam (internal standard) were 6 and 10 min, respectively. Quantitative analysis was operated in selected ion monitoring (SIM) and positive ion mode using target ions at [M + H]+ m/z 284.9 for diazepam and [M + Na]+ m/z 342.9 for lorazepam, respectively. The lower limit of quantification (LLOQ) was 1.2 ng mL−1 and a linear range of 1.2–150 ng mL−1 with correlation coefficients (r 2) of 0.9968. The intra- and inter-day relative standard deviation was <5 and < 10%, respectively. The accuracy values were higher than 95%. The method is simple, sensitive and repeatable, and has been successfully applied to pharmacokinetics studies of lorazepam-loaded mocroemulsions after intranasal administration in rabbit.