Walker Scott, Iazzetta John, Law Shirley
, MScPhm, is Coordinator of Quality Control and Research, Department of Pharmacy, Sunnybrook Health Sciences Centre, North York, Ontario, and Associate Professor, University of Toronto, Toronto, Ontario.
Can J Hosp Pharm. 2009 Mar;62(2):135-41. doi: 10.4212/cjhp.v62i2.442.
The pantoprazole product available in Canada for IV administration has recently been reformulated to include ethylenediaminetetra-acetic acid (EDTA). The purpose of this study was to determine if the chemical stability of pantoprazole for injection containing EDTA (PANTO IV), admixed in polyvinyl chloride (PVC) minibags at concentrations of 0.16 mg/mL and 0.80 mg/mL in 5% dextrose in water (D5W) or 0.9% sodium chloride for injection (normal saline [NS]) and stored at 4°C or 23°C, could be extended beyond the manufacturer's expiry period of 24 hours.
Sodium pantoprazole was reconstituted in NS or D5W, and 32 PVC minibags were prepared, 16 containing pantoprazole at a nominal concentration of 0.16 mg/mL (8 in NS, 8 in D5W) and 16 containing pantoprazole at a nominal concentration of 0.80 mg/mL (8 in NS, 8 in D5W). Half of the minibags for each diluent-concentration combination were stored at 4°C and half at room temperature (23°C). The concentration of pantoprazole in each minibag was determined by a validated, stability-indicating liquid chromatographic method on study days 0, 1, 2, 4, 7, 9, 11, 14, and 21.
Analysis of variance revealed differences in the percentage of drug remaining in relation to temperature (p < 0.001), study day (p = 0.001), concentration (p = 0.007), and diluent (p = 0.008).
Solutions of pantoprazole in D5W with concentration between 0.16 mg/mL and 0.80 mg/mL can be stored for a maximum of 11 days at 4°C plus an additional 6 h at 23°C. The saline solutions degraded more slowly, and pantoprazole admixtures in NS with concentration between 0.16 mg/mL and 0.80 mg/mL can be stored for 20 days at 4°C plus an additional 6 h at 23°C. Under these conditions, more than 90% of the initial concentration will remain (with 95% confidence).
加拿大可用于静脉注射的泮托拉唑产品最近进行了重新配方，加入了乙二胺四乙酸（EDTA）。本研究的目的是确定含有EDTA的注射用泮托拉唑（PANTO IV），以0.16 mg/mL和0.80 mg/mL的浓度在5%葡萄糖注射液（D5W）或0.9%氯化钠注射液（生理盐水[NS]）中混合，并在4°C或23°C下储存时，其化学稳定性是否能延长至超过制造商规定的24小时有效期。
将泮托拉唑钠在NS或D5W中复溶，制备32个PVC小袋，其中16个含有标称浓度为0.16 mg/mL的泮托拉唑（8个在NS中，8个在D5W中），16个含有标称浓度为0.80 mg/mL的泮托拉唑（8个在NS中，8个在D5W中）。每种稀释剂 - 浓度组合的小袋一半储存在4°C，一半储存在室温（23°C）。在研究的第0、1、2、4、7、9、11、14和21天，通过经过验证的、能指示稳定性的液相色谱法测定每个小袋中泮托拉唑的浓度。
方差分析显示，药物残留百分比在温度（p < 0.001）、研究天数（p = 0.001）、浓度（p = 0.007）和稀释剂（p = 0.008）方面存在差异。
浓度在0.16 mg/mL至0.80 mg/mL之间的泮托拉唑D5W溶液在4°C下最多可储存11天，在23°C下可额外储存6小时。盐溶液降解较慢，浓度在0.16 mg/mL至0.80 mg/mL之间的泮托拉唑NS混合液在4°C下可储存20天，在23°C下可额外储存6小时。在这些条件下，初始浓度的90%以上将保留（95%置信度）。
