Analytical Methods for Metformin Estimation

Patel, Durgawati; Kumar, Pranab; Sharma, Swapnil; Dwivedi, Jaya

doi:10.1080/10408347.2017.1304200

Cited by 14 publications

(5 citation statements)

References 68 publications

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“…The aim of the present study was to develop a GC-MS method for the determination of the concentration of metformin in urine and serum samples of the previous study [13]. Our results are in full accordance with the pharmacokinetics of chronically orally administered metformin to healthy and ill patients [10][11][12][16][17][18][19][20][21][22][23]. Much higher metformin concentrations were measured in the urine samples compared to the respective serum samples of patients who received metformin.…”

Section: Discussionsupporting

confidence: 78%

“…Metformin (N,N-dimethylguanylguanidine) is a widely used anti-diabetic drug and possesses many pharmacological actions exerted in part by not fully elucidated mechanisms. Because of the great interest in metformin, several different analytical methods have been developed and used in clinical pharmacokinetic studies and clinical trials in the past decades [10][11][12][16][17][18][19][20][21][22][23]. GC-based methods have been among the first used for the analysis of metformin in biological fluids [16].…”

Section: Discussionmentioning

confidence: 99%

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Stable-Isotope Dilution GC–MS Measurement of Metformin in Human Serum and Urine after Derivatization with Pentafluoropropionic Anhydride and Its Application in Becker Muscular Dystrophy Patients Administered with Metformin, l-Citrulline, or Their Combination

et al. 2022

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Metformin (N,N-dimethylguanylguanidine) is one of the most prescribed drugs with pleiotropic, exerted in part by not fully elucidated mechanisms of action. We developed and validated a gas chromatography–mass spectrometry (GC–MS) method for the quantitative analysis of metformin (metformin-d0) in 10-µL aliquots of human serum and urine using N,N-[dimethylo-2H6]guanylguanidine (metformin-d6) as the internal standard. The method involves evaporation of the samples to dryness, derivatization with pentafluoropropionic (PFP) anhydride in ethyl acetate (30 min, 65 °C), and extraction into toluene. The negative-ion chemical ionization GC–MS spectra of the PFP derivatives contain a single intense ion with mass-to-charge (m/z) ratios of m/z 383 for metformin-d0 and m/z 389 for metformin-d6. Our results suggest that all amine/imine groups of metformin-d0 and metformin-d6 are converted to their N,N,N-tripentafluoropropionyl derivatives, which cyclize to form a symmetric triazine derivative, of which the non-ring amine group is amidated. Quantification was performed by selected-ion monitoring (SIM) of m/z 383 and m/z 389. Upon validation, the method was applied to determine serum and urine metformin concentrations in 19 patients with Becker muscular dystrophy (BMD). Serum and urine samples were collected at baseline (Visit I), after six weeks of supplementation (Visit II) with metformin (3 × 500 mg/d; metformin group; n = 10) or l-citrulline (3 × 1500 mg/d; citrulline group; n = 9) followed by a six-week supplementation with 3 × 500 mg/d of metformin plus 3 × 1500 mg/d l-citrulline. At Visit I, the metformin concentration in the serum and urine was very low in both groups. The metformin concentrations in the serum and urine of the patients who first took metformin (MET group) were higher at Visit II and Visit III. The metformin concentration in the serum and urine samples of the patients who first took l-citrulline (CITR group) were higher at Visit III. The serum and urine concentrations of metformin were insignificantly lower in the CITR group at Visit III. The mean fractional excretion (FE) rate of metformin was 307% (Visit II) and 322% (Visit III) in the MET group, and 290% in the CITR group (Visit III). This observation suggests the accumulation of metformin in the kidney and its secretion in the urine. The GC–MS is suitable to measure reliably circulating and excretory metformin in clinical settings.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Stable-Isotope Dilution GC–MS Measurement of Metformin in Human Serum and Urine after Derivatization with Pentafluoropropionic Anhydride and Its Application in Becker Muscular Dystrophy Patients Administered with Metformin, l-Citrulline, or Their Combination

et al. 2022

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“…The analytical methods for metformin evaluation were researched in the literature through scientific articles, as well as in official compendium. [7,9,18,25,39,47,62] Table 1 shows the analytical methods described in the literature for the determination of metformin. HPLC-EM/EM Column C18 (100 mm £ 2 mm; 3 mm) with pre-column varian (0.20 mm x 0.20 mm; 5 mm) at 30 C; MP: water: acetonitrile: formic acid (55:45:0.048, v/v/%); flow 0.3 mL/min Uninformed Operated in positive mode and electrospray ionization (ESI)…”

Section: Methodsmentioning

confidence: 99%

Metformin: A Review of Characteristics, Properties, Analytical Methods and Impact in the Green Chemistry

Trindade

Kogawa

Salgado

2017

Critical Reviews in Analytical Chemistry

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Diabetes mellitus (DM) is considered a public health problem. The initial treatment consists of improving the lifestyle and making changes in the diet. When these changes are not enough, the use of medication becomes necessary. The metformin aims to reduce the hepatic production of glucose and is the preferred treatment for type 2. The objective is to survey the characteristics and properties of metformin, as well as hold a discussion on the existing analytical methods to green chemistry and their impacts for both the operator and the environment. For the survey, data searches were conducted by scientific papers in the literature as well as in official compendium. The characteristics and properties are shown, also, methods using liquid chromatography techniques, titration, absorption spectrophotometry in the ultraviolet and the infrared region. Most of the methods presented are not green chemistry oriented. It is necessary the awareness of everyone involved in the optimization of the methods applied through the implementation of green chemistry to determine the metformin.

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“…Metformin from biological probes was analyzed using high per formance liquid chromatography in combination with mass spec trometry [25].…”

Section: Metformin Serum Levelsmentioning

confidence: 99%

Metformin Associated Lactic Acidosis in Clinical Practice – A Case Series

Schädle

Tschritter

Kellerer

2020

Exp Clin Endocrinol Diabetes

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Aims The aim of this case report is to specify the frequency and mortality of Metformin-Associated Lactic Acidosis (MALA) in emergency medicine, as the diagnosis seems to occur more often than estimated. Methods To identify the subjects, we developed screening criteria for MALA. We measured the serum metformin concentration to confirm the diagnosis in all patients fulfilling these criteria. Retrospectively the patients were grouped according to individual risk (according to a defined risk score) and the application of renal replacement therapy. Results From 2013 until 2018 we were able to identify 11 MALA patients revealing a frequency of 1:4,000 emergency patients. Six patients survived and five died in the follow-up. All three patients in the high-risk group died although all of them received renal replacement therapy. In the low-risk group (three patients, one with renal replacement therapy), all patients survived, while in the intermediate-risk group (five patients, one with renal replacement therapy) three patients survived and two died. Additional severe comorbidities also contributed to mortality. Conclusions Every patient matching the screening criteria of acute renal failure, lactic acidosis and continued intake of metformin can be considered a potential MALA case. A risk score assessment which includes severe comorbidities may help to identify high-risk individuals and should be evaluated in larger studies.To prevent MALA, patients should be trained to immediately interrupt their own metformin use when showing signs of volume depletion. Physicians should be aware of the additional risk factors such as co-medication with diuretics, ACE (angiotensin converting enzyme) ACE inhibitors and NSAIDs (non steroidal anti inflammatory drugs).

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Analytical Methods for Metformin Estimation

Cited by 14 publications

References 68 publications

Stable-Isotope Dilution GC–MS Measurement of Metformin in Human Serum and Urine after Derivatization with Pentafluoropropionic Anhydride and Its Application in Becker Muscular Dystrophy Patients Administered with Metformin, l-Citrulline, or Their Combination

Stable-Isotope Dilution GC–MS Measurement of Metformin in Human Serum and Urine after Derivatization with Pentafluoropropionic Anhydride and Its Application in Becker Muscular Dystrophy Patients Administered with Metformin, l-Citrulline, or Their Combination

Metformin: A Review of Characteristics, Properties, Analytical Methods and Impact in the Green Chemistry

Metformin Associated Lactic Acidosis in Clinical Practice – A Case Series

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