Liquid chromatography-tandem mass spectrometric assay for pravastatin and two isomeric metabolites in mouse plasma and tissue homogenates

Sparidans, Rolf W.; Iusuf, Dilek; Schinkel, Alfred H.; Schellens, Jan H.M.; Beijnen, Jos H.

doi:10.1016/j.jchromb.2010.08.015

Cited by 15 publications

(10 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The methods for pravastatin quantification in mouse plasma, liver, kidney, gastrocnemius, soleus, and urine were adapted from previously published methods [21]. Pravastatin (catalog #P4498) and 3-α-isopravastatin (catalog #H952310) were purchased from Sigma Aldrich and Toronto Research Chemicals (Ontario, Canada), respectively.…”

Section: Methodsmentioning

confidence: 99%

Synergistic interaction between genetics and disease on pravastatin disposition

Clarke

Hardwick

Lake

et al. 2014

Journal of Hepatology

View full text Add to dashboard Cite

Background & Aims A genome wide association study and multiple pharmacogenetic studies have implicated the hepatic uptake transporter organic anion transporting polypeptide-1B1 (OATP1B1) in the pharmacokinetics and musculoskeletal toxicity of statin drugs. Other OATP uptake transporters can participate in the transport of pravastatin, partially compensating for the loss of OATP1B1 in patients carrying the polymorphism. Nonalcoholic steatohepatitis (NASH) in humans and in a diet-induced rodent model alter the expression of multiple OATP transporters. Methods To determine how genetic alteration in one Oatp transporter can interact with NASH-associated changes in Oatp expression we measured the disposition of intravenously administered pravastatin in Slco1b2 knockout (Slco1b2−/−) and wild-type (WT) mice fed either a control or a methionine and choline deficient (MCD) diet to induce NASH. Results Genetic loss of Oatp1b2, the rodent ortholog of human OATP1B transporters, caused a modest increase in pravastatin plasma concentrations in mice with healthy livers. Although a diet-induced model of NASH decreased the expression of multiple hepatic Oatp transporters, it did not alter the disposition of pravastatin compared to WT control mice. In contrast, the combination of NASH-associated decrease in compensatory Oatp transporters and Oatp1b2 genetic loss caused a synergistic increase in plasma area under the curve (AUC) and tissue concentrations in kidney and muscle. Conclusions Our data show that NASH alters the expression of multiple hepatic uptake transporters which, due to overlapping substrate specificity among the OATP transporters, may combine with the pharmacogenetic loss of OATP1B1 to increase the risk of statin-induced adverse drug reactions.

show abstract

Section: Methodsmentioning

confidence: 99%

Synergistic interaction between genetics and disease on pravastatin disposition

Clarke

Hardwick

Lake

et al. 2014

Journal of Hepatology

View full text Add to dashboard Cite

show abstract

“…In case of pravastatin, two peaks were detected in some analytical runs (see Figure 2). Pravastatin was described to be prone to isomerization under acidic conditions [27]. Therefore, the second peak was expected to be a pravastatin artifact formed during sample preparation, which was not detectable during analysis of neat standard solution.…”

Section: Discussionmentioning

confidence: 99%

“…The second peak eluted later (1.2 min) and had a lower abundance and smaller peak area in comparison to pravastatin (0.9 min). The second peak was most probably a pravastatin isomer formed during sample preparation and was quantified together with the pravastatin if present [27].…”

Section: Methods Development and Validationmentioning

confidence: 99%

Method development for quantitative determination of seven statins including four active metabolites by means of high-resolution tandem mass spectrometry applicable for adherence testing and therapeutic drug monitoring

Wagmann

Hemmer

Caspar

et al. 2019

Clinical Chemistry and Laboratory Medicine (CCLM)

View full text Add to dashboard Cite

BackgroundStatins are used to treat and prevent cardiovascular diseases (CVDs) by reducing the total serum cholesterol concentration. Unfortunately, dose-related side effects and sub-optimal response, attributed to non-adherence amongst others, were described. Therefore, a fast and sensitive liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) method for adherence testing and therapeutic drug monitoring of all currently marketed statins and their active metabolites in human blood plasma should be developed, validated and tested for applicability.MethodsAtorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin, as well as ortho- and para-hydroxy-atorvastatin, lovastatin hydroxy acid and simvastatin hydroxy acid were included and several internal standards (IS) tested. Validation was performed according to the guideline of the European Medicines Agency including selectivity, carry-over, accuracy, precision, matrix effects, dilution integrity and analyte stability. Finally, applicability was tested using 14 patient samples submitted for regular toxicological analysis.ResultsDue to an analytical interference of atorvastatin-d5, diazepam-d5 and pentobarbital-d5 were chosen as IS for positive and negative ionization mode, respectively. All statins and metabolites fulfilled the validation acceptance criteria except for fluvastatin, which could not be quantified reliably and reproducibly, most probably due to instability. Analyses of human plasma samples revealed concentrations of statins and metabolites below the reference plasma concentrations in the case of eight patients. However, nothing was known concerning patients’ adherence and time between intake and sampling.ConclusionsAn LC-HRMS/MS method for identification and quantification of atorvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin and four active metabolites was successfully developed and applicability demonstrated.

show abstract

“…Numerous methods have been developed and validated for detection/ estimation of Pravastatin in plasma including high performance liquid chromatography with UV detection, LC/MS/MS [5][6][7][8][9][10][11][12][13][14]. In addition to pravastatin, 3α-iso-pravastatin and 6-epi-pravastatin could also be quantified in some assays [15,16].…”

Section: Introductionmentioning

confidence: 99%

Method Development and Validation for the Determination of Pravastatin in Human Plasma by Lc-Ms/Ms

Lian¹,

Joshi²,

Piatkivskyi³

et al. 2017

J Bioanal Biomed

View full text Add to dashboard Cite

A simple, rapid, sensitive and selective liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for the quantification of pravastatin in human plasma. Pravastatin-D3 was used as an internal standard. The analyte was extracted from human plasma samples by liquid-liquid extraction technique. Due to the presence of isobaric metabolites, 3α-iso-pravastatin and 6-epi-pravastatin, chromatographic conditions were optimized, with a C18 column by using a mixture of 0.1% acetic acid in water and acetonitrile/methanol (43:57, v/v) as the mobile phase at a flow rate of 0.6 mL/min. The calibration curve obtained was linear (r2 ≥ 0.9900) over the concentration range of 0.500-500 ng/mL. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The method was suitable for supporting clinical studies.

show abstract

Liquid chromatography-tandem mass spectrometric assay for pravastatin and two isomeric metabolites in mouse plasma and tissue homogenates

Cited by 15 publications

References 28 publications

Synergistic interaction between genetics and disease on pravastatin disposition

Synergistic interaction between genetics and disease on pravastatin disposition

Method development for quantitative determination of seven statins including four active metabolites by means of high-resolution tandem mass spectrometry applicable for adherence testing and therapeutic drug monitoring

Method Development and Validation for the Determination of Pravastatin in Human Plasma by Lc-Ms/Ms

Contact Info

Product

Resources

About