Quantification of Lansoprazole in Oral Suspension by Ultra-High-Performance Liquid Chromatography Hybrid Ion-Trap Time-of-Flight Mass Spectrometry

An LC-MS/MS method was developed and validated to be used as a stability indicating assay for the study of a 3？mg/mL lansoprazole oral suspension. The method utilizes a UPLC (ultra-performance liquid chromatography) column and unique mass spectrometric detection (ion-trap time-of-flight (IT-TOF)) to achieve a sensitive (LOD 2？ng/mL), accurate, and reproducible quantification of lansoprazole. This method reports an intraday and interday coefficient of variation of 2.98 ± 2.17% ( for each concentration for each day) and 3.07 ± 0.89% ( for each concentration), respectively. Calibration curves (5–25？μg/mL) were found to be linear with an value ranging from 0.9972 to 0.9991 on 4 different days. Accuracy of the assay, expressed as % error, ranged from 0.30 to 5.22%. This method is useful for monitoring the stability of lansoprazole in oral suspension. 1. Introduction A significant problem in pediatric pharmacotherapy is the lack of commercially available liquid formulations. Proton pump inhibitors (PPIs) are a class of drugs that are routinely used in children; however, stability data for extemporaneous liquid formulations are not readily available for many of these compounds. In a prospective study performed by Lugo et al., which included 21 children’s hospitals, an oral suspension of lansoprazole was the number one reported extemporaneous formulation prepared in the inpatient setting [1]. In the study, 19 of 21 hospitals surveyed reported using a 3？mg/mL lansoprazole oral suspension; however, there are limited data regarding the stability of this formulation [1]. Compromised stability, in regard to commercial and extemporaneous formulations, is defined as loss of more than 10% of the active ingredient [2]. While the lack of stability of lansoprazole in acidic media (such as apple juice) has been clearly demonstrated [3], the studies examining the stability in a basic suspension (prepared in 8.4% sodium bicarbonate) are conflicting. According to a study by DiGiacinto et al., the reported stability of lansoprazole suspension was eight hours at 22°C and 14？days at 4°C [4]. In contrast, a study performed by Phillips et al. revealed a stability of 4？weeks when lansoprazole was stored in amber plastic vials under refrigeration and 2？weeks at room temperature [5]. Thus, the commonly accepted stability of lansoprazole suspension prepared in 8.4%？sodium bicarbonate is 14？days [6]. A few reports of lansoprazole quantification by LC-MS/MS can be found in the literature. Hishinuma et al. [7] measured lansoprazole and rabeprazole in human serum for applications in