TY - JOUR
T1 - Determination of O6-Methylguanine in dried blood spot of breast cancer patients after cyclophosphamide administration
AU - Harahap, Yahdiana
AU - Tanujaya, Athalia Theda
AU - Nurahman, Farhan
AU - Vianney, Aurelia Maria
AU - Purwanto, Denni Joko
N1 - Funding Information:
This work was supported by the Directorate of Research and Community Services Universitas Indonesia , Depok, Indonesia.
Publisher Copyright:
© 2021
PY - 2021/7
Y1 - 2021/7
N2 - 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 O6-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 O6-Methylguanine. Analysis of O6-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 O6-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 O6-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.
AB - 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 O6-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 O6-Methylguanine. Analysis of O6-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 O6-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 O6-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.
KW - Cyclophosphamide
KW - Dried blood spot (DBS)
KW - O-Methylguanine
KW - Secondary cancer
KW - UPLC-MS/MS
UR - http://www.scopus.com/inward/record.url?scp=85110374842&partnerID=8YFLogxK
U2 - 10.1016/j.heliyon.2021.e07558
DO - 10.1016/j.heliyon.2021.e07558
M3 - Article
AN - SCOPUS:85110374842
SN - 2405-8440
VL - 7
JO - Heliyon
JF - Heliyon
IS - 7
M1 - e07558
ER -
