Owen Heather J, Gonyon Thomas M, Green John-Bruce D, Patel Dipa H, Eilert Jan Y, Gripman Laura L, Wyrwa Steve T
J Pediatr Pharmacol Ther. 2019 Jan-Feb;24(1):45-52. doi: 10.5863/1551-6776-24.1.45.
Calcium and phosphate incompatibility in parenteral nutrition formulations remains a critical concern for patient safety. This study examined calcium phosphate solubility for 2-in-1 admixtures prepared using 2 commercially available pediatric amino acid solutions (Premasol, Baxter Healthcare Corp; or Trophamine, B. Braun Medical Inc), applying identical test methods, storage conditions, and acceptance criteria.
Parenteral 2-in-1 admixtures included amino acid; dextrose; static concentrations of sodium, potassium, and magnesium, and varying concentrations of calcium (0-60 mEq/L), phosphate (15-50 mmol/L), and cysteine. Three replicate samples were stored for 48 hours at 40°C ± 2°C and then visually inspected for particulate matter, evaluated for subvisible particulate matter, when particulate matter was noted, microscopic examination was performed to confirm the presence of calcium phosphate crystals. Pass criteria were: all replicates free of visible particulate matter related to calcium phosphate crystals and particle counts below US Pharmacopeia <788> limits.
Premasol and Trophamine generated identical calcium phosphate curves for 2% amino acid formulations containing 20% dextrose with/without cysteine, and similar curves for the 1% or 3% amino acid formulations containing 10% or 20% dextrose with/without cysteine. Calcium phosphate particles were identified in failed samples by scanning electron microscopy/energy dispersive X-ray spectroscopy. Calcium phosphate solubility was higher in formulations containing cysteine 40 mg/g amino acid vs. cysteine 20 mg/g amino acid and in cysteine 20 mg/g amino acid vs. no cysteine.
Admixtures made with 1%, 2%, or 3% Premasol or Trophamine have essentially equivalent calcium phosphate solubility curves when tested with identical methods, storage conditions, and acceptance criteria.
肠外营养制剂中的钙磷不相容性仍是患者安全的关键问题。本研究使用两种市售儿科氨基酸溶液（普瑞马索，百特医疗保健公司；或特罗法明，贝朗医疗公司）制备二合一混合液，采用相同的测试方法、储存条件和验收标准，检测磷酸钙的溶解度。
肠外二合一混合液包括氨基酸、葡萄糖、钠、钾和镁的静态浓度，以及不同浓度的钙（0 - 60 mEq/L）、磷（15 - 50 mmol/L）和半胱氨酸。将三个重复样品在40°C ± 2°C下储存48小时，然后目视检查是否有颗粒物，若发现有颗粒物，则评估亚可见颗粒物，并进行显微镜检查以确认磷酸钙晶体的存在。通过标准为：所有重复样品均无与磷酸钙晶体相关的可见颗粒物，且颗粒计数低于美国药典<788>规定的限值。
对于含20%葡萄糖且有/无半胱氨酸的2%氨基酸制剂，普瑞马索和特罗法明产生相同的磷酸钙曲线；对于含10%或20%葡萄糖且有/无半胱氨酸的1%或3%氨基酸制剂，二者产生相似的曲线。通过扫描电子显微镜/能量色散X射线光谱法在不合格样品中鉴定出磷酸钙颗粒。含40 mg/g氨基酸半胱氨酸的制剂中磷酸钙溶解度高于含20 mg/g氨基酸半胱氨酸的制剂，含20 mg/g氨基酸半胱氨酸的制剂中磷酸钙溶解度高于不含半胱氨酸时的溶解度。
当采用相同方法、储存条件和验收标准进行测试时，用1%、2%或3%普瑞马索或特罗法明制成的混合液具有基本等效的磷酸钙溶解度曲线。
