Table 1.

Main findings of each study.

Author (Year)	Study Design	Study Topic	Main Findings
Harahap et al. (2020) [11]	Cross-sectional	Analysis of 3-HPMA using LC-MS/MS	-Hematuria still can be occurred in breast cancer patient after cyclophosphamide and MESNA administration -Subjects who were positive for hematuria had high levels of 3-HPMA
Moein et al. (2017) [32]	Review	Bioanalytical method development	-LC-MS/MS produces good analysis results with very high selectivity and sensitivity.
Zhao et al. (2017) [35]	Experimental	Urine as a biological sample for bioanalysis	-Urine is an important biological sample in bioanalysis because urinary proteomics studies have identified various biomarkers for urogenital diseases.
Drouin et al. (2020) [36]	Review	Urine sample preparation for bioanalysis	-For bioanalysis purpose, urine can be prepared by dilute and shoot method.
Xu et al. (2012) [37]	Review	Urine sample preparation for bioanalysis	-For bioanalysis purpose, urine can be prepared by solid phase extraction method.
Novák et al. (2016) [38]	Review	Urine sample preparation for bioanalysis	-For bioanalysis purpose, urine can be prepared by protein precipitation method.
Tully et al. (2018) [39]	Animal research study	3-HPMA analysis in urine samples	-Urine can be a good biological sample to carry out an analysis of 3-HPMA levels.
Harahap et al. (2020) [40]	Experimental	Bioanalytical method for analyzing the 3-HPMA concentration in urine samples	-Dilution and formic acid acidification preparation sample method provided a good result of the analysis of 3-HPMA levels in urine with a LLOQ value of 40.0 ng/ml. -ESI + ion mode LC-MS/MS provided a sensitive and specific analysis of 3-HPMA in urine.
Carmella et al. (2007) [41]	Cross-sectional	Bioanalytical method for analyzing the 3-HPMA concentration in urine samples	-Solid phase extraction with 2% NH4OH preparation sample method provided a good result of the analysis of 3-HPMA levels in urine with a low LLOQ value of 0.9 ng/ml. -LC-APCI-MS/MS-SRM provided a sensitive and specific analysis of 3-HPMA in urine.
Yan et al. (2010) [42]	Experimental	Bioanalytical method for analyzing the 3-HPMA concentration in urine samples	-Dilution with ammonium formate preparation sample method provided a good result of the analysis of 3-HPMA levels in urine with a LLOQ value of 40.0 ng/ml. -ESI- ion mode LC-MS/MS provided a sensitive and specific analysis of 3-HPMA in urine.
Gao et al. (2020) [43]	Case report	Single nucleotide polymorphism (SNP) study	-A lot of genotype data can be found in high-density SNP.
Bruijins et al. (2018) [45]	Experimental	DNA extraction methods	-DNA extracted from buccal swab samples could not be completely analyzed because some types of swabs bind DNA effectively.
Ng et al. (2018) [46]	Experimental	DNA extraction methods	-Urine samples only contain a few nucleated cells and are not ideal for being used as a source of DNA.
Martins et al. (2015) [47]	Experimental	DNA extraction methods from biological samples	-Hair samples were not a good sample for DNA extraction because they have a low concentration of noncoding DNA and/or a high level of degradation.
Guha et al. (2017) [48]	Experimental	DNA extraction methods from biological samples	-Blood samples contain a good amount of nucleated white blood cells. -There are many protocols regarding DNA isolation from blood that have been published.
Kaewkhao et al. (2019) [49]	Experimental	DNA extraction methods from biological samples	-Blood samples must be handled carefully. -Blood samples were not good to be applied to children if large volume of samples were needed.
Nakajima et al. (2007) [51]	Cross-sectional	CYP2B6 polymorphisms method analysis	-CYP2B6 Genotyping can be focused on exons 4 and 5. The selected primers were 2B6∗9S and 2B6∗9-AS for c.516G > T and primers 2B6∗4-S and 2B6∗4-AS for c.785A > G. -The process of the PCR step included denaturation at 94 °C for 3 minutes, amplification by denaturation at 94 °C for 30 seconds, annealing for 30 seconds, and extension/elongation at 72 °C for 30–90 seconds for 30 cycles. The final extension was carried out at 72 °C for 5 minutes.
Kumar et al. (2019) [12]	Case report	Cyclophosphamide side effect	-There was a reported cases of hemorrhagic cystitis incidence after the first cycle of therapy regimen of cyclophosphamide and docetaxel at a dose of 600 mg/m2 and 75 mg/m2 on a woman with stage IIA breast cancer, 63 years old.
Saito et al. (2018) [52]	Cross-sectional	Cyclophosphamide side effect	-MESNA and strong hydration were considered effective to prevent cyclophosphamide-induced hemorrhagic cystitis.
Teles et al. (2017) [53]	Review	Cyclophosphamide side effect	-MESNA has side effects, such as nausea and vomiting.
Doshi et al. (2019) [54]	Review	Cyclophosphamide side effect	-In patients who were receiving high doses of cyclophosphamide, MESNA and hydration were not enough to prevent hemorrhagic cystitis.
Shu et al. (2016) [55]	Cross-sectional	CYP2B6 polymorphisms on cyclophosphamide metabolism	-CYP450 enzymes in heart catalyzed cyclophosphamide hydroxylation.
Hedrich et al. (2016) [56]	Review	CYP2B6 polymorphisms	-CYP2B6 plays a role in the metabolism of 2–10% of common anticancer drugs.
Zanger et al. (2013) [57]	Review	CYP2B6 polymorphisms	-There were several factors that made the CYP2B6 varied, such as non-genetic factors, genetic polymorphism, ability to be induced, and inhibition by various compounds.
Lang et al. (2001) [58]	Cross-sectional	CYP2B6 polymorphisms on cyclophosphamide metabolism	-9 SNPs that produced 5 amino acid substitutions were identified, which were CYP2B6∗2 (R22C), CYP2B6∗3 (S259R), CYP2B6∗4 (K262R), CYP2B6∗5 (R487C), CYP2B6∗6 (Q172H and K262R), and CYP2B6∗7 (Q172H, K262, R762).
Lamba et al. (2003) [59]	Cross-sectional	CYP2B6 polymorphisms on cyclophosphamide metabolism	-Another CYP2B6 variants, CYP2B6∗8 (K139E) and CYP2B6∗9 (Q172H), were introduced.
Lang et al. (2004) [22]	Cross-sectional	CYP2B6 polymorphisms on cyclophosphamide metabolism	-Another CYP2B6 variants, CYP2B6∗10 (Q21L and R22C), CYP2B6∗11 (M46V), CYP2B6∗12 (G99E), CYP2B6∗13 (K139E, Q172H, and K262R), CYP2B6∗14 (R140Q), and CYP2B6∗15 (I391N), were introduced.
Xie et al. (2003) [60]	Cross-sectional	CYP2B6 polymorphisms on cyclophosphamide metabolism	-CYP2B6∗6 allele can increase the bioactivation of cyclophosphamide.
Xie et al. (2006) [61]	Cross-sectional	CYP2B6 polymorphisms on cyclophosphamide metabolism	-CYP2B6∗6 allele can increase cyclophosphamide hydroxylation.
Kirchheiner et al. (2003) [62]	Cross-sectional	CYP2B6 polymorphisms on cyclophosphamide metabolism	-CYP2B6∗6 allele can increase several drugs hydroxylation process.