Determination of methotrexate in serum by high-performance liquid chromatography

Aboleneen, Hoda; Simpson, J.; Backes, D.

doi:10.1016/0378-4347(95)00580-3

Cited by 33 publications

(9 citation statements)

References 23 publications

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“…However these methods have some drawbacks, such as complex derivitization procedures for sample preparation (Licea-Perez et al, 2007;Liu et al, 2010), absence of a validated method in matrices other than plasma (Kosovec et al, 2008) and longer run times (van Kuilenburg et al, 2006). Similarly for MTX, HPLC methods with UV (Aboleneen et al, 1996;Sartori et al, 2008;Sparreboom et al, 1999) or fluorescence detectors (Lobo and Balthasar, 2003) have been reported. Recent studies have reported LOQ values of 3.9 ng/mL (Blakeley et al, 2009), which are comparable to our LOQ of 15.6 ng/mL; however, concentrations as low as 3.9 ng/mL are rarely observed for MTX in a PK study spread over 24 h (den Boer et al, 2012).…”

Section: Lc Methods Developmentmentioning

confidence: 99%

Pharmacokinetic application of a bio‐analytical LC‐MS method developed for 5‐fluorouracil and methotrexate in mouse plasma, brain and urine

Ganti

Walker

Nagar

2013

Biomedical Chromatography

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In the past we have reported significant cognitive deficits in mice receiving 5-fluorouracil in combination with low-dose methotrexate. To explain such interactions, a pharmacokinetic study was designed. A sensitive bio-analytical method was therefore developed and validated for 5-fluorouracil and methotrexate in mouse plasma, brain and urine with liquid chromatography coupled to a single quadrupole mass spectrometer. Chromatographic separation was accomplished by Agilent® Zorbax® SB-C18 column, with isocratic elution (5 mM ammonium acetate and methanol, 70:30, %v/v) at a flow rate of 300 μL/min. The limit of quantitation for both drugs was 15.6 ng/mL (plasma and brain) and 78.1 ng/mL (urine), with interday and intraday precision and accuracy ≤15% and a total run time of 6 min. This bio-analytical method was used for the pharmacokinetic characterization of 5-fluorouracil and methotrexate in mouse plasma, brain and urine over a period of 24 h. This method allowed characterization of the brain concentrations of 5-fluorouracil over a period of 24 h.

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Section: Lc Methods Developmentmentioning

confidence: 99%

Pharmacokinetic application of a bio‐analytical LC‐MS method developed for 5‐fluorouracil and methotrexate in mouse plasma, brain and urine

Ganti

Walker

Nagar

2013

Biomedical Chromatography

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“…However, most published methods for quantification of MTX and its metabolites did not employ the usage of internal standard. Among the methods with an internal standard, theophylline, 8-chlorotheophylline, aminopterin or OHM, the metabolite of MTX was used [23][24][25][26]. Ideally, the isotopically labeled internal standard is preferred in multistep sample preparation procedure.…”

Section: Sample Preparation Proceduresmentioning

confidence: 99%

Determination of erythrocyte methotrexate polyglutamates by liquid chromatography/tandem mass spectrometry after low-dose methotrexate therapy in Chinese patients with rheumatoid arthritis

Yao

Ren

et al. 2012

Journal of Chromatography B

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“…is the preferred assay technique. Many methods have been published [ 72–76] with lower limits of ≈0.02–0.03 μm, but none offers the one step, fully automated advantages of EMIT. H.p.l.c.…”

Section: Methotrexate (Mtx)mentioning

confidence: 99%

Therapeutic drug monitoring of antimetabolic cytotoxic drugs

Lennard

1999

Brit J Clinical Pharma

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Therapeutic drug monitoring is not routinely used for cytotoxic agents. There are several reasons, but one major drawback is the lack of established therapeutic concentration ranges. Combination chemotherapy makes the establishment of therapeutic ranges for individual drugs difficult, the concentration-effect relationship for a single drug may not be the same as that when the drug is used in a drug combination. Pharmacokinetic optimization protocols for many classes of cytotoxic compounds exist in specialized centres, and some of these protocols are now part of large multicentre trials. Nonetheless, methotrexate is the only agent which is routinely monitored in most treatment centres. An additional factor, especially in antimetabolite therapy, is the existence of pharmacogenetic enzymes which play a major role in drug metabolism. Monitoring of therapy could include assay of phenotypic enzyme activities or genotype in addition to, or instead of, the more traditional measurement of parent drug or drug metabolites. The cytotoxic activities of mercaptopurine and fluorouracil are regulated by thiopurine methyltransferase (TPMT) and dihydropyrimidine dehydrogenase (DPD), respectively. Lack of TPMT functional activity produces life-threatening mercaptopurine myelotoxicity. Very low DPD activity reduces fluorouracil breakdown producing severe cytotoxicity. These pharmacogenetic enzymes can influence the bioavailability, pharmacokinetics, toxicity and efficacy of their substrate drugs.

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Determination of methotrexate in serum by high-performance liquid chromatography

Cited by 33 publications

References 23 publications

Pharmacokinetic application of a bio‐analytical LC‐MS method developed for 5‐fluorouracil and methotrexate in mouse plasma, brain and urine

Pharmacokinetic application of a bio‐analytical LC‐MS method developed for 5‐fluorouracil and methotrexate in mouse plasma, brain and urine

Determination of erythrocyte methotrexate polyglutamates by liquid chromatography/tandem mass spectrometry after low-dose methotrexate therapy in Chinese patients with rheumatoid arthritis

Therapeutic drug monitoring of antimetabolic cytotoxic drugs

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