Harahap Yahdiana, Tanujaya Athalia Theda, Nurahman Farhan, Vianney Aurelia Maria, Purwanto Denni Joko
Bioavailability/Bioequivalence Laboratory, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia.
Faculty of Pharmacy, Republic of Indonesia Defense University, Bogor, 16810, Indonesia.
Heliyon. 2021 Jul 13;7(7):e07558. doi: 10.1016/j.heliyon.2021.e07558. eCollection 2021 Jul.
Cyclophosphamide is a nitrogen mustard class of drugs that are often used in cancer chemotherapy. However, the use of Cyclophosphamide in high doses over a long period has been shown to increase the risk of developing secondary cancer. This can be indicated by the formation of mutagenic DNA adducts, such as O-Methylguanine. Therefore, this adduct can be used as a biomarker for secondary cancer in patients receiving Cyclophosphamide. Bio sampling was carried out by using the Dried Blood Spot (DBS) method, followed by DNA extraction by using QIAamp DNA mini kit, and acid hydrolysis to obtain O-Methylguanine. Analysis of O-Methylguanine was performed by using the UPLC-MS/MS instrument with the conditions developed by Vianney, Harahap, & Suryadi (2021). Partial validation was carried out before the analysis. The results obtained from the calibration curve, accuracy, and precision validation test met the FDA requirements. The analysis method was then implemented in 16 breast cancer patients who received the Cyclophosphamide regimen. The O-Methylguanine was successfully detected and quantified in all of the samples in the range of 0.55-6.66 ng/mL. It shows that the O-Methylguanine accumulation in cancer patients receiving Cyclophosphamide is very likely to occur and the analysis method proposed by Vianney, Harahap, & Suryadi (2021) is potential to be used for Therapeutic Drug Monitoring in this group of patients.
环磷酰胺是一类氮芥类药物，常用于癌症化疗。然而，长期大剂量使用环磷酰胺已被证明会增加患继发性癌症的风险。这可以通过诱变DNA加合物的形成来表明，例如O-甲基鸟嘌呤。因此，这种加合物可作为接受环磷酰胺治疗患者继发性癌症的生物标志物。通过使用干血斑（DBS）方法进行生物采样，随后使用QIAamp DNA微型试剂盒进行DNA提取，并进行酸水解以获得O-甲基鸟嘌呤。使用Vianney、Harahap和Suryadi（2021年）开发的条件，通过超高效液相色谱-串联质谱仪（UPLC-MS/MS）对O-甲基鸟嘌呤进行分析。在分析之前进行了部分验证。校准曲线、准确度和精密度验证测试获得的结果符合美国食品药品监督管理局（FDA）的要求。然后将该分析方法应用于16名接受环磷酰胺治疗方案的乳腺癌患者。在所有样本中成功检测并定量了O-甲基鸟嘌呤，其含量范围为0.55-6.66 ng/mL。这表明接受环磷酰胺治疗的癌症患者中很可能会发生O-甲基鸟嘌呤的积累，并且Vianney、Harahap和Suryadi（2021年）提出的分析方法有可能用于该组患者的治疗药物监测。
