Erram Satyajit V, Fanska Cindy B, Asif Muhammad
Analytical Development, Dey L.P., Napa, CA 94558, USA.
J Pharm Biomed Anal. 2006 Mar 3;40(4):864-74. doi: 10.1016/j.jpba.2005.08.021. Epub 2005 Oct 21.
An isocratic reversed-phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated for the determination of albuterol sulfate and six of its related substances in albuterol sulfate inhalation solution, 0.5% (w/v). The separation was achieved using a YMC phenyl column (250 mm x 4.6 mm ID, 5 microm fitted with a direct connect YMC phenyl guard column (20 mm x 4 mm ID) maintained at ambient conditions, and a mobile phase of 25 mM monobasic potassium phosphate (pH 3.0) and methanol (95:5, v/v). The mobile phase flow rate was 1.5 mL/min and the detection wavelength was 225 nm. Albuterol is quantitated versus an external standard. The method was capable of resolving six of the seven known albuterol-related substances. Bis-ether albuterol, a drug substance process related impurity, is retained on the column due to its different hydrophilic character. The related substances are determined by area percent. However, a correction factor of 1.6 is applied for the determination of albuterol aldehyde, a potential impurity and a degradation product, since its molar absorptivity is about 1.6 times that of albuterol. The limits of detection and quantitation for albuterol and six of its related substances ranged between 0.01 and 0.21% of the assay concentration of 0.3 mg/mL as albuterol base. The method was found to be linear for albuterol over the range of 50-150% of the active label claim. The method was also found to be linear for the six related substances over the range 0.05-0.5%. No interferences from the blank, placebo (formulation matrix), related substances or force-degraded placebo samples were observed for the determination of the active or the individual related substances. The method was found to be accurate, precise, linear, specific, sensitive, rugged, robust, and stability-indicating.
已开发并验证了一种等度反相高效液相色谱（RP-HPLC）方法，用于测定0.5%（w/v）硫酸沙丁胺醇吸入溶液中硫酸沙丁胺醇及其六种相关物质。使用YMC苯基柱（250 mm×4.6 mm内径，5 µm，配有直接连接的YMC苯基保护柱（20 mm×4 mm内径））在环境条件下进行分离，流动相为25 mM磷酸二氢钾（pH 3.0）和甲醇（95:5，v/v）。流动相流速为1.5 mL/min，检测波长为225 nm。沙丁胺醇相对于外标进行定量。该方法能够分离七种已知沙丁胺醇相关物质中的六种。双醚沙丁胺醇是一种原料药工艺相关杂质，由于其不同的亲水性而保留在柱上。相关物质通过面积百分比测定。然而，由于沙丁胺醇醛的摩尔吸光率约为沙丁胺醇的1.6倍，因此在测定潜在杂质和降解产物沙丁胺醇醛时应用了1.6的校正因子。沙丁胺醇及其六种相关物质的检测限和定量限在以沙丁胺醇碱计的0.3 mg/mL测定浓度的0.01%至0.21%之间。发现该方法在活性标签声明的50-150%范围内沙丁胺醇呈线性。还发现该方法在六种相关物质的0.05-0.5%范围内呈线性。在测定活性成分或各个相关物质时，未观察到空白、安慰剂（制剂基质）、相关物质或强制降解安慰剂样品的干扰。该方法被发现准确、精密、线性、特异、灵敏、耐用、稳健且具有稳定性指示性。
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