PMID- 34746455
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231108
IS  - 2405-8440 (Print)
IS  - 2405-8440 (Electronic)
IS  - 2405-8440 (Linking)
VI  - 7
IP  - 10
DP  - 2021 Oct
TI  - The correlation between the level of 3-hydroxypropyl mercapturic acid, CYP2B6 
      polymorphisms, and hematuria occurrences after cyclophosphamide administration 
      and its bioanalytical methods: A systematic review.
PG  - e08126
LID - 10.1016/j.heliyon.2021.e08126 [doi]
LID - e08126
AB  - BACKGROUND: Cyclophosphamide (CPA) is a cytotoxic prodrug that needs to be 
      metabolized by cytochrome P450 enzymes, like CYP2B6. Unfortunately, CYP2B6 is a 
      very polymorphic enzyme and can cause a change in 3-hydroxypropyl mercapturic 
      acid (3-HPMA), the most found CYP metabolite in urine levels. Change in 3-HPMA 
      levels can also indicate the level change in its precursor, acrolein, which is 
      responsible for the hematuria incidence after CPA administration.This review's 
      purpose is to obtain a conclusion about the optimal 3-HPMA analysis method in 
      urine after the administration of cyclophosphamide using liquid 
      chromatography-tandem mass spectrometry (LC-MS/MS) through literature review from 
      previous studies. Also, this review was written to examine the relationship 
      between levels of 3-HPMA in urine, polymorphisms of CYP2B6 enzymes, and the 
      incidence of hematuria after cyclophosphamide administration in cancer patients. 
      METHODS: Major databases, such as Universitas Indonesia's library database 
      ScienceDirect, PubMed/Medline, Frontiers Media, and Google Scholar database, were 
      used to find both published and unpublished studies without a time limit until 
      2020. Studies on pharmacokinetics, pharmacodynamics, drug therapy monitoring of 
      cyclophosphamide, bioanalysis, and polymerase chain reaction (PCR) published in 
      Indonesian and English were included. Meanwhile, non-related studies or studies 
      written in other languages besides Indonesian and English were excluded. Two 
      independent reviewers screened the titles, abstracts, and full-text manuscripts. 
      Data obtained from eligible sources were used to answer the purpose of this 
      review in a narrative form. RESULTS: The authors found 436 related studies from 
      various databases and websites. Then, the authors narrowed it down into 62 pieces 
      of literature by removing the duplicates and reviewing the abstracts and 
      full-text manuscripts. Out of 62 sources, the authors found 30 studies that 
      explained 3-HPMA analysis using LC/MS-MS, CYP2B6 polymorphisms, and hematuria 
      occurrences. The authors used those 30 studies to build a conclusion regarding 
      the purpose of this study. We strengthened the results with some additional 
      information from the other 32 eligible sources. CONCLUSIONS: The authors conclude 
      that according to literature searches from previous studies, the optimal 3-HPMA 
      analysis method in urine after cyclophosphamide administration using LC-MS/MS is 
      using triple quadrupole LC-MS/MS; source of positive ion electrospray ionization 
      (ESI); mobile phase combination of 0.1% formic acid in water (A) - 0.1% formic 
      acid in acetonitrile (90:10 v/v) (B); the Acquity(R) BEH C18 column (2.1 x 100 mm; 
      1.7 mum); injection volume of 10 mul; flow rate of 0.2 ml/minute; gradient elution 
      method. Detection was carried out using mass spectrometry with m/z ratio of 
      222.10 > 90 for 3-HPMA and m/z 164.10 > 122 for n-acetylcysteine (NAC). The 
      optimum sample preparation method is acidification and dilution ratio of 1:5 v/v. 
      Also, there is a relationship between 3-HPMA levels, CYP2B6 polymorphisms, and 
      the occurrences of hematuria after the administration of cyclophosphamide, which 
      is a type of CYP2B6 polymorph, namely CYP2B6 *6, can increase cyclophosphamide 
      hydroxylation so that it can increase the levels of acrolein and 3-HPMA, as its 
      metabolites, and risk of hematuria. ETHICS AND DISSEMINATION: This research does 
      not use human participants, human data, or human tissue for being directly 
      studied for the review. Therefore, ethics approval and consent to participate are 
      not applicable. REGISTRATION: This research has not been registered yet.
CI  - (c) 2021 The Authors.
FAU - Harahap, Yahdiana
AU  - Harahap Y
AD  - Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, West Java, Indonesia.
AD  - Faculty of Military Pharmacy, Indonesia Defense University, Bogor, West Java, 
      Indonesia.
FAU - Nurahman, Farhan
AU  - Nurahman F
AD  - Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, West Java, Indonesia.
FAU - Purwanto, Denni Joko
AU  - Purwanto DJ
AD  - Faculty of Military Pharmacy, Indonesia Defense University, Bogor, West Java, 
      Indonesia.
FAU - Yanuar, Arry
AU  - Yanuar A
AD  - Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, West Java, Indonesia.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20211004
PL  - England
TA  - Heliyon
JT  - Heliyon
JID - 101672560
PMC - PMC8551512
OTO - NOTNLM
OT  - 3-hydroxypropyl mercapturic acid (3-HPMA)
OT  - CYP2B6
OT  - Cyclophosphamide (CPA)
OT  - Hematuria
OT  - Hemorrhagic cystitis
COIS- The authors declare no conflict of interest.
EDAT- 2021/11/09 06:00
MHDA- 2021/11/09 06:01
PMCR- 2021/10/04
CRDT- 2021/11/08 06:53
PHST- 2021/06/07 00:00 [received]
PHST- 2021/07/21 00:00 [revised]
PHST- 2021/09/30 00:00 [accepted]
PHST- 2021/11/08 06:53 [entrez]
PHST- 2021/11/09 06:00 [pubmed]
PHST- 2021/11/09 06:01 [medline]
PHST- 2021/10/04 00:00 [pmc-release]
AID - S2405-8440(21)02229-5 [pii]
AID - e08126 [pii]
AID - 10.1016/j.heliyon.2021.e08126 [doi]
PST - epublish
SO  - Heliyon. 2021 Oct 4;7(10):e08126. doi: 10.1016/j.heliyon.2021.e08126. eCollection 
      2021 Oct.