Determination of total mycophenolic acid and its glucuronide metabolite using liquid chromatography with ultraviolet detection and unbound mycophenolic acid using tandem mass spectrometry

Patel, Chirag; Mendonza, Anisha E.; Akhlaghi, Fatemeh; Majid, Oneeb; Trull, Andrew K.; Lee, Terry; Holt, David W.

doi:10.1016/j.jchromb.2004.10.004

Cited by 58 publications

(37 citation statements)

References 18 publications

(17 reference statements)

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“…13 The concentration of free MPA was assessed using ultrafiltration followed by liquid chromatography/mass spectrometry/mass spectrometry in plasma. 14 Concentrations of iohexol 15 and acetaminophen 6 were measured by HPLC-UV. All methods were developed in-house and validated according to the guidelines set by the U.S. Food and Drug Administration.…”

Section: Determination Of Drug Concentrationsmentioning

confidence: 99%

Effect of Diabetes Mellitus on Mycophenolate Sodium Pharmacokinetics and Inosine Monophosphate Dehydrogenase Activity in Stable Kidney Transplant Recipients

Patel¹,

Richman²,

Yang³

et al. 2007

Therapeutic Drug Monitoring

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Effect of diabetes mellitus on mycophenolic acid (MPA) pharmacokinetics and catalytic activity of inosine monophosphate dehydrogenase (IMPDH) was investigated in maintenance kidney transplant recipients. Demographically matched diabetic (n = 9) and nondiabetic (n = 9) patients were included in a 12-hour open-label, steady-state study after oral administration of entericcoated mycophenolate sodium. Concentrations of total MPA and free MPA, MPA-glucuronide, and acyl-MPA-glucuronide were measured and oral acetaminophen absorption was used as a marker for gastric-emptying rate. Median (range) of MPA area under the curve 0-12 was 36.7 (range, 16.4-116.4) mg * h/L in diabetic and 48.2 (range, 34.9-80.1) mg * h/L in nondiabetic patients (P = 0.49). All other primary pharmacokinetic parameters, including time to maximum concentration, for total or unbound MPA as well as MPA metabolites were comparable. In contrast, IMPDH activity was 17.5 ± 2.8 versus 46.6 ± 2.5 nmol XMP/h/mg protein in diabetics and nondiabetics, respectively (P < 0.0001) and was significantly lower in the diabetics irrespective of concomitant therapy with cyclosporine or tacrolimus. This study demonstrated that diabetes does not alter MPA pharmacokinetics when administered as enteric-coated mycophenolate sodium; however, IMPDH activity appeared to be significantly lower in patients with diabetes independent of the unbound or total concentrations of MPA. Further investigations are warranted to investigate the regulation of IMPDH enzyme in patients with diabetes.

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Section: Determination Of Drug Concentrationsmentioning

confidence: 99%

Effect of Diabetes Mellitus on Mycophenolate Sodium Pharmacokinetics and Inosine Monophosphate Dehydrogenase Activity in Stable Kidney Transplant Recipients

Patel¹,

Richman²,

Yang³

et al. 2007

Therapeutic Drug Monitoring

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“…The limit of quantiˆcation of 0.05 mg/ml for MPA in this HPLC-UV method was more sensitive than that of previous methods. [16][17][18]21,22,25) Application Chromatograms of plasma samples collected from a representative patient at 2 and 12 hours after oral administration of MMF are shown in Figs. 1(C) and 1(D), respectively.…”

Section: Calibration Curvementioning

confidence: 99%

“…14) Some methods allow quantitation only of MPA concentration, [15][16][17][18] and several permit the simultaneous determination of MPA and MPAG. [19][20][21][22][23][24][25][26] Most of these methods are time-consuming extraction step and require larger sample volumes, special techniques and complicated procedures for the assay. So a simpler assay method is highly expected.…”

Section: Introductionmentioning

confidence: 99%

Quantification and 24-hour Monitoring of Mycophenolic Acid by High-Performance Liquid Chromatography in Japanese Renal Transplant Recipients

et al. 2006

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We developed a rapid, simple, and sensitive high-performance liquid chromatography method with UV detection for the quantitative determination of mycophenolic acid (MPA) in human plasma. MPA and the internal standard (naproxen) were separated using a mobile phase of 0.04 M H 3 PO 4 -acetonitrile-methanol (3：3：4 v/v/v) over a CAP-CELL PAK C18 MG column. A ‰ow-rate of 0.5 ml/min was used at ambient temperature and sample detection was carried out at 254 nm. The assay required only 100 ml of plasma and involved liquid-liquid extraction, which gave high recovery (＞94％). The lower limit of quantiˆcation for MPA was 0.05 mg/ml. Inter-and intra-day coe‹cients of variation were less than 9.6％ and accuracies were within 9.3％. Additionally, we validated this method in 24-hour monitoring of plasma MPA concentrations after mycophenolate mofetil (MMF) morning and evening administration in 40 Japanese renal transplant recipients with 1.5 g/day MMF. The time to reach the maximum (11.7 mg/ml) and second peak (4.5 mg/ml) of MPA after morning 0.75 g MMF administration was 2.6 h and 9.0 h, and time to reach maximum (10.5 mg/ml) after evening 0.75 g administration was 4.0 h.

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“…Many assays have been described that use HPLC-UV (11,12,13 ) or mass spectrometry (6,14,15 ) for the quantification of MPA and/or MPAG. The use of HPLC-UV methods to measure AcMPAG has been reported (11,12 ), but the use of mass spectrometry has not.…”

mentioning

confidence: 99%

Quantification by Liquid Chromatography Tandem Mass Spectrometry of Mycophenolic Acid and Its Phenol and Acyl Glucuronide Metabolites

Brandhorst¹,

Streit

Goetze

et al. 2006

Clinical Chemistry

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Determination of total mycophenolic acid and its glucuronide metabolite using liquid chromatography with ultraviolet detection and unbound mycophenolic acid using tandem mass spectrometry

Cited by 58 publications

References 18 publications

Effect of Diabetes Mellitus on Mycophenolate Sodium Pharmacokinetics and Inosine Monophosphate Dehydrogenase Activity in Stable Kidney Transplant Recipients

Effect of Diabetes Mellitus on Mycophenolate Sodium Pharmacokinetics and Inosine Monophosphate Dehydrogenase Activity in Stable Kidney Transplant Recipients

Quantification and 24-hour Monitoring of Mycophenolic Acid by High-Performance Liquid Chromatography in Japanese Renal Transplant Recipients

Quantification by Liquid Chromatography Tandem Mass Spectrometry of Mycophenolic Acid and Its Phenol and Acyl Glucuronide Metabolites

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