目的 采用超高效液相色譜質(zhì)譜聯(lián)用（UPLC-MS/MS）法同時測定異環(huán)磷酰胺原料藥中主成分及2種有關(guān)物質(zhì)。方法 采用ACQUITY UPLC^® HSS T3（100 mm×2.1 mm，1.8 μm）色譜柱，以甲醇（A）-5 mmol·L-1碳酸氫銨溶液（B）為流動相進(jìn)行梯度洗脫，對異環(huán)磷酰胺原料藥中的異環(huán)磷酰胺、雜質(zhì)G、雜質(zhì)E進(jìn)行分離，體積流量為0.3 mL·min^-1，進(jìn)樣量為10 μL，柱溫為30℃，質(zhì)子離子源ESI，正離子模式下以多反應(yīng)監(jiān)測方式（MRM）進(jìn)行定量分析。結(jié)果 異環(huán)磷酰胺、雜質(zhì)E、雜質(zhì)G的線性范圍分別1.00～50.00、1.00～50.00、0.01～0.5 ng·mL^-1，線性關(guān)系良好，r均大于0.999 4；且該方法的儀器精密度、重復(fù)性良好，異環(huán)磷酰胺的回收率為98.1%～101.7%、RSD為0.40%～1.73%，雜質(zhì)E的回收率為96.1%～111.1%、RSD為0.67%～2.34%，雜質(zhì)G的回收率為93.7%～108.3%、RSD為2.2%～7.6%，符合標(biāo)準(zhǔn)。原料藥中的異環(huán)磷酰胺質(zhì)量分?jǐn)?shù)為97.1～98.5%，雜質(zhì)E均未檢出，雜質(zhì)G在1501批次檢出量最高，為0.009 25%，雜質(zhì)E和G未超千分之一限度。結(jié)論 建立的UPLC-MS/MS法靈敏度較高、重復(fù)性好，為異環(huán)磷酰胺原料藥的質(zhì)量控制提供了一種可行的分析方法，適用于該產(chǎn)品的質(zhì)量控制。

Objective To use liquid chromatography-mass spectrometry (UPLC-MS/MS) to simultaneously determine the principal components and two related substances in ifosfamide API. Methods The ACQUITY UPLC^® HSS T3 (100 mm × 2.1 mm, 1.8 μm) column was used to perform gradient elution of methanol (A) -5 mmol·L^-1 ammonium bicarbonate (B) as the mobile phase, and ifosfamide, impurity G and impurity E in ifosfamide API were separated with a flow rate of 0.3 mL·min^-1, an injection volume of 10 μL, a column temperature of 30 ℃, and a proton ion source ESI. Quantification in positive ion mode in multi-reaction monitoring mode (MRM). Results The linear ranges of ifosfamide, impurity E and impurity G were 1.00-50.00、1.00-50.00、0.01-0.5 ng·mL^-1 respectively, with good linear relationships and correlation coefficients greater than 0.994, and the instrument precision and repeatability of the method were good. The recoveries of isocyclophosphamide were 98.1%-101.7% with RSD of 0.40%-1.73%. The recovery of impurity E was 96.1%-111.1% with RSD of 0.67%-2.34%. The recoveries of impurity G were 93.7%-108.3% with RSD of 2.2%-7.6%. The mass fraction of ifosfamide in the raw material was 97.1%-98.5%, and impurity E had not been detected. The detection amount of impurity G in batch 1501 is 0.009 25%, and impurities E and G do not exceed the limit of one thousandth. Conclusion The proposed method has high sensitivity and good repeatability, which provides a feasible analysis method for the quality control of ifosfamide API, which is suitable for the quality control of this product.

R932

江蘇省產(chǎn)教融合一流課程《藥物分析》建設(shè)項目；江蘇海洋大學(xué)專業(yè)學(xué)位研究生課程案例庫建設(shè)項目（YJSZY202102）；江蘇海洋大學(xué)2023年一流課程立項；連云港市政策引導(dǎo)產(chǎn)學(xué)研項目（CYX2202）