Determination of two HMG‐CoA reductase inhibitors, pravastatin and pitavastatin, in plasma samples using liquid chromatography–tandem mass spectrometry for pharmaceutical study

Abstract

We developed a method for determining pravastatin or pitavastatin, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, in plasma using liquid chromatography and tandem mass spectrometry (LC-MS/MS). Pravastatin, pitavastatin and the internal standard fluvastatin were extracted from plasma with solid-phase extraction columns and eluted with methanol. After drying the organic layer, the residue was reconstituted in mobile phase (acetonitrile:water, 90:10, v/v) and injected onto a reversed-phase C(18) column. The isocratic mobile phase was eluted at 0.2 mL/min. The ion transitions recorded in multiple reaction monitoring mode were m/z 423 --> 101, 420 --> 290 and 410 --> 348 for pravastatin, pitavastatin and fluvastatin, respectively. The coefficient of variation of the assay precision was less than 12.4%, the accuracy exceeded 89%. The limit of detection was 1 ng/mL for all analytes. This method was used to measure the plasma concentration of pitavastatin or pravastatin from healthy subjects after a single 4 mg oral dose of pitavastatin or 40 mg oral dose of pravastatin. This is a very simple, sensitive and accurate analytic method to determine the pharmacokinetic profiles of pitavastatin or pravastatiny.

Development and validation of a liquid chromatography–tandem mass spectrometric assay for pitavastatin and its lactone in human plasma and urine

“…It needed a long chromatographic run time (>25 min) and time-consuming sample pretreatments. Recently, two LC-MS/MS methods employing electrospray ionization source have been published [11,12]. However, both the methods have not described simultaneous determinations of both the open and closed forms of the drug.…”

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

“…Precisions and deviations of the accuracy had to meet the required ±15% (±20% for the lower limit of quantification (LLQ)) [26][27][28]. Precisions for pravastatin and is isomeric metabolites were in the same order as in previously reported assays for human plasma and serum [17][18][19][20][21][22][23][24][25].…”

“…However, since 1998 LC/MS/MS assays [16][17][18][19][20][21][22][23][24][25] have become available for pravastatin. In addition to pravastatin, the 3 ␣-isomeric metabolite [19][20][21][22][23][24] (Fig.…”

“…Positive electrospray ionization was used for both assays capable of quantifying the lactone metabolite, negative ionization with APCI [20,21,24] or ESI [17][18][19]25] was used in other LC/MS/MS assays. All these LC/MS/MS methods [17][18][19][20][21][22][23][24][25] use reversed-phase chromatography and solid-phase extraction on a reversed-phase sorbent. Bioanalytical LC/MS/MS assays for samples of other species have only been reported, concisely, for mice [9][10][11] and rat [5] using a simple protein precipitation procedure without the ability to quantify metabolites.…”

Spectrofluorometric Determination of Certain Antihyperlipidemic Agents in Bulk and Pharmaceutical Preparations

“…Similarly, a survey of analytical literature for the determination of EZE either in biological samples or pharmaceutical preparations revealed methods based on HPLC [10][11][12][13] and LC/MS/MS [14,15] for its determination in human plasma, UV-spectrophotometric determination of combination with other drug [16] and stabilityindicating LC [17,18]. Besides, different analytical methods for the determination of PIT have been reported, including spectrophotometry [19], high-performance thin-layer chromatography [20], and LC/MS/MS for its determination in human plasma [21][22][23][24]. Spectrofluorometry has long been applied in the field of pharmaceutical analysis of many drugs [25][26][27][28] because of the higher sensitivity than is attainable in absorption spectrophotometry.…”