Development and validation of a reversed-phase liquid chromatographic method with fluorescence detection for the study of Saquinavir pharmacokinetics in rat plasma

Pathak, Shriram M.; Kumar, A. S. Kiran; Subramanian, G.; Udupa, N.

doi:10.1016/j.aca.2007.05.028

Cited by 13 publications

(11 citation statements)

References 18 publications

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“…Moreover, we noticed a double peak phenomenon in plasma SQV profiles in the presence and absence of RESV. Similar double peaking phenomena were also documented in multiple SQV PK studies involving rats35,37,38 and humans 39–41. Several physiological mechanisms can generate the double peaking phenomenon, including enterohepatic recycling, gastric emptying, small intestinal transit, and site-specific absorption 42.…”

Section: Discussionsupporting

confidence: 74%

Effects of resveratrol on P-glycoprotein and cytochrome P450 3A in vitro and on pharmacokinetics of oral saquinavir in rats

Li¹,

Liu²,

Zhang³

et al. 2016

DDDT

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BackgroundThe intestinal cytochrome P450 3A (CYP 3A) and P-glycoprotein (P-gp) present a barrier to the oral absorption of saquinavir (SQV). Resveratrol (RESV) has been indicated to have modulatory effects on P-gp and CYP 3A. Therefore, this study was to investigate the effects of RESV on P-gp and CYP 3A activities in vitro and in vivo on oral SQV pharmacokinetics in rats.MethodsIn vitro, intestinal microsomes were used to evaluate RESV effect on CYP 3A-mediated metabolism of SQV; MDR1-expressing Madin–Darby canine kidney (MDCKII-MDR1) cells were employed to assess the impact of RESV on P-gp-mediated efflux of SQV. In vivo effects were studied using 10 rats randomly assigned to receive oral SQV (30 mg/kg) with or without RESV (20 mg/kg). Serial blood samples were obtained over the following 24 h. Concentrations of SQV in samples were ascertained using high-performance liquid chromatography-tandem mass spectrometry analysis.ResultsRESV (1–100 μM) enhanced residual SQV (% of control) in a dose-dependent manner after incubation with intestinal microsomes. RESV (1–100 μM) reduced the accumulation of SQV in MDCKII-MDR1 cells in a concentration-dependent manner. A double peaking phenomenon was observed in the plasma SQV profiles in rats. The first peak of plasma SQV concentration was increased, but the second peak was reduced by coadministration with RESV. The mean AUC0–∞ of SQV was slightly decreased, with no statistical significance probably due to the high individual variation.ConclusionRESV can alter the plasma SQV concentration profiles, shorten the Tmax of SQV. RESV might also cause a slight decrease tendency in the SQV bioavailability in rats.

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Section: Discussionsupporting

confidence: 74%

Effects of resveratrol on P-glycoprotein and cytochrome P450 3A in vitro and on pharmacokinetics of oral saquinavir in rats

Li¹,

Liu²,

Zhang³

et al. 2016

DDDT

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“…Statistical analysis was performed using Microsoft Excel 2000 while pharmacokinetic software, 'Ramkin', based on a noncompartment model, was used to calculate the [AUC] from the serum drug concentration vs time profiles. These results, C max, AUC 0-t and AUC 0-∞ , could not be compared with those of Pathak et al (2007) because the dose of SQV used for those studies was different (20 mg/kg). However, the parameters like T max (3.8 and 1.9) and t 1/2 (3.1and 3.6) were found to be in good agreement.…”

Section: Application To Pharmacokinetic Studiescontrasting

confidence: 46%

“…Kakuda and Falcon (2006) studied the effect of food and ranitidine on SQV pharmacokinetics and gastric pH in healthy volunteers. Pathak et al (2007) developed a validated RP-LC fluorescence method for SQV in rat plasma. Sekar et al (2007) and Singh et al (2008) developed pharmacokinetic methods for SQV and explained the interaction between SQV and darunavir in HIV-negative volunteers and infected subjects.…”

Section: Saquinavir (2s)-n-{(2s3r)-4-[(3s)-3-(tert-butylcarbamoyl)-mentioning

confidence: 99%

Ionic liquid‐based dispersive liquid–liquid microextraction followed by RP‐HPLC determination of saquinavir in rat serum: application to pharmacokinetics

Ramisetti

Nimmu

Naidu

2014

Biomedical Chromatography

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An ionic liquid-based dispersive liquid-liquid microextraction followed by RP-HPLC determination of the most commonly prescribed protease inhibitor, saquinavir, in rat plasma was developed and validated. The effects of different ionic liquids, dispersive solvents, extractant/disperser ratio and salt concentration on sample recovery and enrichment were studied. Among the ionic liquids investigated, 1-butyl-3-methylimidazolium hexafluorophosphate was found to be most effective for extraction of saquinavir from rat serum. The recovery was found to be 95% at an extractant/disperser ratio of 0.43 using 1-butyl-3-methylimidazolium hexafluorophosphate and methanol as extraction and dispersive solvents. The recovery was further enhanced to 99.5% by addition of 5.0% NaCl. A threefold enhancement in detection and quantification limits was achieved, at 0.01 and 0.03 µg/mL, compared with the conventional protein precipitation method. A linear relationship was observed in the range of 0.035-10.0 µg/mL with a correlation coefficient (r(2) ) of 0.9996. The method was validated and applied to study pharmacokinetics of saquinavir in rat serum.

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“…A thorough literature survey revealed the availability of only a few analytical methods like HPLC and LC/MS/MS for the determination of SQM in biological samples . However, no analytical method has been reported for the determination of SQM and its DPs in bulk and pharmaceutical formulations.…”

mentioning

confidence: 99%

“…Hyphenated techniques such as liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) combined with accurate mass measurement have been established as promising techniques and widely used in the identification and structural elucidation of DPs. [13][14][15] A thorough literature survey revealed the availability of only a few analytical methods like HPLC [16] and LC/MS/MS for the determination of SQM in biological samples. [17][18][19] However, no analytical method has been reported for the determination of SQM and its DPs in bulk and pharmaceutical formulations.…”

mentioning

confidence: 99%

Identification of degradation products of saquinavir mesylate by ultra‐high‐performance liquid chromatography/electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry and its application to quality control

Thummar

Patel

Petkar

et al. 2017

Rapid Comm Mass Spectrometry

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Rationale Saquinavir mesylate (SQM) is an antiviral drug used for the treatment of HIV infections. The identification and characterization of all degradation products are essential for achieving the quality in pharmaceutical product development and also for patient safety. Methods The drug was subjected to hydrolytic (HCl, NaOH and water), oxidative (H2O2), photolytic (UV and fluorescence light) and thermal (dry heat) forced degradation conditions as per ICH guidelines. The best chromatographic separation of the drug and all degradation products (DPs) was achieved on a CSH‐Phenyl Hexyl column (100 × 2.1 mm, 1.7 μm) with ammonium acetate (10 mM, pH 5.0) and methanol as mobile phase in gradient mode at a flow rate of 0.28 mL/min. Results Nine DPs were obtained under various forced degradation conditions. All the DPs were characterized by using ultra‐high‐performance liquid chromatography/electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry (UHPLC/ESI‐QTOF MS/MS) and the degradation pathway of the drug was justified by mechanistic explanations. The main DPs were formed by amide hydrolysis, conversion into diastereomers, an N‐oxide and dehydration as well as oxidation of the alcohol from the drug. The method was validated and can be used in a quality control (QC) laboratory to assure the quality of SQM in bulk and finished formulations. Conclusions A simple UHPLC/photodiode array (PDA) method was developed and successfully transferred to UHPLC/ESI‐Q‐TOF MS/MS for the identification and characterization of DPs. Very interestingly, diastereomeric DPs were obtained and successfully resolved by the chromatographic method. Copyright © 2017 John Wiley & Sons, Ltd.

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Development and validation of a reversed-phase liquid chromatographic method with fluorescence detection for the study of Saquinavir pharmacokinetics in rat plasma

Cited by 13 publications

References 18 publications

Effects of resveratrol on P-glycoprotein and cytochrome P450 3A in vitro and on pharmacokinetics of oral saquinavir in rats

Effects of resveratrol on P-glycoprotein and cytochrome P450 3A in vitro and on pharmacokinetics of oral saquinavir in rats

Ionic liquid‐based dispersive liquid–liquid microextraction followed by RP‐HPLC determination of saquinavir in rat serum: application to pharmacokinetics

Identification of degradation products of saquinavir mesylate by ultra‐high‐performance liquid chromatography/electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry and its application to quality control

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