A LC-MS/MS method for simultaneous estimation of a novel anti-diabetic combination of saxagliptin and dapagliflozin using a polarity switch approach: application to <i>in vivo</i> rat pharmacokinetic study

Surendran, Shruti; Paul, David; Pokharkar, Sunil; Deshpande, Abhijeet; Giri, Sanjeev; Satheeshkumar, N.

doi:10.1039/c8ay02087f

Cited by 9 publications

(7 citation statements)

References 17 publications

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“…A solid phase extraction procedure was applied for sample clean-up. The technique demonstrated high linearity in the range of 0.2 to 80 ng/mL for SAX and 5 to 2000 ng/mL for DAP [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of drug interactions of saxagliptin with sildenafil in healthy volunteers

Mansour

ElBorolossy

Shaheen

et al. 2022

Eur J Clin Pharmacol

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Purpose The purpose of this study is to investigate the effect of sildenafil a CYP3A4 substrate and inhibitor on the pharmacokinetics and safety of saxagliptin. Methods Eighteen healthy volunteers were recruited in sequential; single-center study to determine pharmacokinetic parameters of saxagliptin and sildenafil, and (AUC0-∞), (AUC0-t); Cmax; tmax; t½, ke; ka were measured using validated LC–MS/MS method. Therapeutic doses were given as follows: Sildenafil 50 mg single dose on day one, then washout period from day two till day eight. Saxagliptin 5 mg once/day was given from day 9 till day 12; then on day 13, the two drugs were co-administered. Blood samples for pharmacokinetic analysis were collected on days 1 and 13 for sildenafil and on days 12 and 13 for saxagliptin. Results Saxagliptin ratios of T/R and 90% CI were 132.1% (122.7–142.3) for AUC0–t, and 167.6% (154.6–181.8) for Cmax. On the other hand, sildenafil pharmacokinetics were not affected. Gmax changed from 93.7 mg/dl to 95.6 mg/dl (P > 0.001) and AUCg0-t from 512.8 ng.h/ml to 532.75 ng.h/ml (P > 0.001) after co-administration of both drugs. Conclusion Sildenafil significantly affected the pharmacokinetic parameters of saxagliptin when co-administered. Registration This trial was registered at clinicaltrials.gov under identifier number: [NCT04170790] in November 2019.

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“…A solid phase extraction procedure was applied for sample clean-up. The technique demonstrated high linearity in the range of 0.2 to 80 ng/mL for SAX and 5 to 2000 ng/mL for DAP [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of drug interactions of saxagliptin with sildenafil in healthy volunteers

Mansour

ElBorolossy

Shaheen

et al. 2022

Eur J Clin Pharmacol

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“…Intern, which consists of saxagliptine and dapagliflozin, is a combination medication for treating type 2 diabetes that has been approved by regulatory organizations. [5] Many HPLC [9][10][11][12][13] and a handful of LC-MS [6][7][8] techniques have been revealed for determining both medications separately and in combination. Phanindra [6] et al and Shruti [7] et al did not use deuterated substances as an internal standard in their published procedures.…”

Section: Introductionmentioning

confidence: 99%

“…[5] Many HPLC [9][10][11][12][13] and a handful of LC-MS [6][7][8] techniques have been revealed for determining both medications separately and in combination. Phanindra [6] et al and Shruti [7] et al did not use deuterated substances as an internal standard in their published procedures. Swapna et al reported a lengthy and laborious process for their liquid-liquid extraction approach.…”

Section: Introductionmentioning

confidence: 99%

Liquid Chromatography-Tandem Mass Spectrometry Assay Method for Estimation of Saxagliptine and Dapagliflozin in Human Plasma

Kommineni¹,

Gupta²,

Panigrahy³

et al. 2022

Journal of Pharmaceutical Negative Results

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There has been much research on both saxagliptin and dapagliflozin. However, only a few HPLC and LC-MS methods that use stable labeled isotopes to measure the amount of a drug alone or in combination with other drugs and have a longer chromatographic run time have been published. A quick and sensitive LC-MS/MS mass spectrometric test method has been made and fully validated to find dapagliflozin and saxagliptin in human plasma simultaneously. Solid-phase extraction on the Cleanert PEP-H extraction cartridge was used to separate the analyte and I.S. from the human plasma. The extracted samples were separated on an Ace Phenyl (150 X 4.6 mm, 5 m) column at a set flow rate of 0.8 mL/min using an isocratic mobile phase of acetonitrile and 5 mM ammonium acetate buffer (70:30 v/v). For dapagliflozin, the calibration curve was linear throughout a range of 0.502-227 ng/mL, while for saxagliptin, the range was 0.103-76.402 ng/mL. The procedure was validated in accordance with standards set by the U.S. Food and Drug Administration, and the outcomes are acceptable.

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“…Such sodium-glucose cotransporters are responsible for reabsorbing glucose into the kidney. [2,3] An extensive literature survey has revealed that there are few methods that are reported for estimation of SAXA and DAPA individually or in combination with other drugs by UV method, [4][5][6][7] reverse phase high performance liquid chromatographic (RP-HPLC) method, [8][9][10][11][12][13][14][15][16] tandem mass spectrometry method, [17] or LC-MS. [18,19] Hence, we propose to develop methods that are more reliable, sensitive, and simple for simultaneous estimation of SAXA and DAPA in bulk as well as a pharmaceutical formulation. In the present work, we developed and validated the UV method and RP-HPLC method for the simultaneous estimation of SAXA hydrochloride and DAPA in bulk drug and its formulation as per ICH guidelines Q2(R1).…”

Section: Introductionmentioning

confidence: 99%

Development and Validation RP-HPLC Method for Simultaneous Estimation of Dapagliflozin and Saxagliptin in Bulk and Pharmaceutical Dosage Form

Nizamuddin¹,

Raju

2022

APJHS

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A simple, precise, sensitive, and rapid reverse phase high performance liquid chromatographic method was developed and validated for simultaneous estimation of Dapagliflozin (DAPA) and Saxagliptin (SAXA) in bulk as well as in tablet formulation according to the ICH guidelines. The chromatographic phase consisted by phosphate buffer: Acetonitrile, pH 4.0 adjusted by glacial acetic acid. The flow rate was adjusted to 0.8 ml/min and UV detection was carried out at 220 nm. Retention time was found to be 2.144 and 3.156 min; respectively. The detector was showed that linear responses over the concentration range 10–24 μg/ml for SAXA and 12–40 μg/ml for DAPA a good correlation coefficient of 0.999. This proposed method is highly sensitive, precise, and accurate which reduces cost of analysis; hence, recommended for routine quality analysis in laboratories.

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A LC-MS/MS method for simultaneous estimation of a novel anti-diabetic combination of saxagliptin and dapagliflozin using a polarity switch approach: application to in vivo rat pharmacokinetic study

Abstract: First LC-MS/MS method for the simultaneous determination of SAX and DAP. The method offers good sensitivity with LLOQ of 0.2 ng mL−1 for SAX and 5 ng mL−1 for DAP.

Cited by 9 publications

References 17 publications

Evaluation of drug interactions of saxagliptin with sildenafil in healthy volunteers

Evaluation of drug interactions of saxagliptin with sildenafil in healthy volunteers

Liquid Chromatography-Tandem Mass Spectrometry Assay Method for Estimation of Saxagliptine and Dapagliflozin in Human Plasma

Development and Validation RP-HPLC Method for Simultaneous Estimation of Dapagliflozin and Saxagliptin in Bulk and Pharmaceutical Dosage Form

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