. Author manuscript; available in PMC: 2018 Aug 15.

Published in final edited form as: J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Jun 19;1060:316–324. doi: 10.1016/j.jchromb.2017.06.028

Table 3.

LC/MS determination of antimetabolite drugs in urine

Parent drug	Sample preparation	Chromatography	Interface/Detection	Target analyte	m/z of mass transition	Limit of Detection	Reference
5-fluorouracil	DNFB derivatization & SPE HLB MeOH/ACN	ZIC-HILIC CHCOONH₄/ACN 2.1 × 100mm, 5μm	ESI/QQQ/MRM^-	α-fluoro-β-alanine d₄-β-alanine	272/182 258/182	1 μg/L	[34]
gemcitabine & metabolite	SPE MeOH	RP C8/gradient CH₃COOH/ACN 4.6 × 150 mm, 5μm	ESI/QQQ/MRM⁺	dFdC 2dFdU 2deC	264/112 265/113 228/112	0.05 μg/L 0.3 μg/L	[35]
methotrexate (MTX)	SPE C18 ethylacetate	RP C18/isocratic CH₃COONH₄/MeOH 4.6 × 150 mm, 5μm	ESI/QQQ/MRM⁺	MTX 7-OH-MTX	455/308 471/324	0.2 μg/L	[36]
methotrexate	SPE-HAX methanol/acetic acid	RP C18/gradient CHCOONH₄/ACN 2.1 × 100 mm, 5μm	ESI/QQQ/MRM⁺	MTX d₃-MTX	455/308 458/311	0.01 μg/L	[28]
methotrexate 7-hydroxy-methotrexate	SPE C18 384-well aqueous CHOOH/MeOH	RP C8/gradient CHCOOH/ACN 2.0 × 10 mm, 5μm	ESI/QQQ/SRM⁺	MTX d₃-MTX 7-OH-MTX d₃ 7-OH-MTX	445/308 458/311 471/191 474/191	1 μg/L 50 μg/L	[37]
methotrexate 7-hydroxy-methotrexate	protein precipitation	RP C18/gradient CHCOOH/ACN 2.1 × 100 mm, 1.9μm	ESI/QQQ/SRM⁺	MTX d₃-MTX 7-OH-MTX	455/308 458/311 471/324	1 μg/L 5 μg/L	[38]

Legend of abbreviations used in Table 3. LC/MS determination of antimetabolite drugs in urine.

ACN: acetonitrile, DNFB: 2,4 dinitrofluorobenzene, ESI: electrospray ionization, dFdC: 2′,2′-difluorodeoxycytidine, 2dFdU: 2′,2′-difluorodeoxyuridine, 2deC: 2′-deoxycytidine, MeOH: methanol, MRM: multiple reaction monitoring, QQQ: triple quadrupole, RP: reversed phase, SPE: solid phase extraction, SPE-HAX: SPE non-polar and strong anion exchange, SPE HLB: SPE hydrophilic-lipophilic balance medium, SRM: selective reaction monitoring, ZIC-HILIC: zwitterionic-hydrophilic interaction chromatography