Morrison Jordan T, Lugo Ralph A, Thigpen Jim C, Brown Stacy D
Department of Pharmaceutical Sciences East Tennessee State University, Johnson City, Tennessee.
J Pediatr Pharmacol Ther. 2013 Apr;18(2):122-7. doi: 10.5863/1551-6776-18.2.122.
The purpose of this study was to examine the stability of a generic lansoprazole product in a 3 mg/mL sodium bicarbonate suspension under room temperature and refrigerated conditions.
Lansoprazole suspensions (3 mg/mL) were prepared in triplicate using an 8.4% sodium bicarbonate vehicle for each storage condition (room temperature and refrigerated). During 1 month, samples from each replicate were periodically removed and analyzed for lansoprazole concentration by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Each sample was spiked with 10 mg/L omeprazole to serve as the internal standard. A positive electrospray LC-MS/MS method was validated over the calibration range of 5 to 25 mg/L using Food and Drug Administration Guidance. The identities of the analyte and internal standard in the samples were verified by monitoring the MS/MS transitions of m/z 370 to m/z 252 and m/z 346 to m/z 198 for lansoprazole and omeprazole, respectively. Additionally, the pH of the suspensions was monitored throughout the study.
The stability of lansoprazole in the oral sodium bicarbonate suspension under refrigeration is compromised prior to what has been previously reported in the literature. Samples kept at room temperature lost >10% of the lansoprazole after 48 hours compared with the refrigerated samples, which maintained integrity up to 7 days. No statistically significant difference was found between the pH of the room temperature and refrigerated suspension samples, indicating that this factor is not the cause for the differences in stability at these two conditions.
This study suggests that the extemporaneously compounded lansoprazole oral suspension prepared in 8.4% sodium bicarbonate should not be stored in plastic oral syringes longer than 48 hours at room temperature and no longer than 7 days when refrigerated. These data indicate an expiration time earlier than that previously reported for the refrigerated product (14 days).
本研究旨在考察一种兰索拉唑仿制药产品在室温及冷藏条件下于3 mg/mL碳酸氢钠混悬液中的稳定性。
针对每种储存条件（室温与冷藏），使用8.4%碳酸氢钠载体一式三份制备兰索拉唑混悬液（3 mg/mL）。在1个月期间，定期从每个重复样品中取出样本，采用液相色谱 - 串联质谱法（LC-MS/MS）分析兰索拉唑浓度。每个样品添加10 mg/L奥美拉唑作为内标。根据美国食品药品监督管理局指南，在5至25 mg/L的校准范围内验证了正电喷雾LC-MS/MS方法。通过分别监测兰索拉唑的m/z 370至m/z 252以及奥美拉唑的m/z 346至m/z 198的MS/MS跃迁，验证样品中分析物和内标的身份。此外，在整个研究过程中监测混悬液的pH值。
与先前文献报道相比，冷藏条件下兰索拉唑在口服碳酸氢钠混悬液中的稳定性受到损害。与冷藏样品相比，室温保存的样品在48小时后兰索拉唑损失超过10%，冷藏样品在7天内保持完整。室温与冷藏混悬液样品的pH值之间未发现统计学上的显著差异，表明该因素不是这两种条件下稳定性差异的原因。
本研究表明，用8.4%碳酸氢钠临时配制的兰索拉唑口服混悬液在室温下于塑料口服注射器中储存不应超过48小时，冷藏时不应超过7天。这些数据表明其有效期比先前报道的冷藏产品（14天）更早。
