Journal of pharmaceutical and biomedical analysis
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J Pharm Biomed Anal · Feb 2019
ReviewNDMA impurity in valsartan and other pharmaceutical products: Analytical methods for the determination of N-nitrosamines.
Batch recalls for valsartan containing pharmaceutical products in July 2018 initiated a discussion on possible contaminations with N-nitrosodimethylamine (NDMA). It appeared that NDMA was generated during synthesis of the active pharmaceutical ingredient (API) from the solvent dimethylformamide (DMF) and the reagent nitrite. Discussion on NDMA as API impurity is extended to other drugs since then. ⋯ However, current availability of this combination is very limited. Alternatively, LC-MS/MS is also performed in NA analysis. An integration of a general test in future pharmacopoeias is suggested due to the toxicological relevance and broader spectrum of possible APIs that may be affected.
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J Pharm Biomed Anal · Feb 2019
Case ReportsReliable and easy-to-use LC-MS/MS-method for simultaneous determination of the antihypertensives metoprolol, amlodipine, canrenone and hydrochlorothiazide in patients with therapy-refractory arterial hypertension.
Therapy-refractory arterial hypertension is defined as a blood pressure (BP) in a subset of patients who fail to achieve BP control despite a three-drug regimen (including a diuretic). Various factors have impact on loss of therapy response. Drug-drug-interactions (DDIs) may cause altered pharmacokinetics (PK) of antihypertensive drugs. Upregulation of activity and expression of cytochrome P450 (CYP) enzymes can result in decreased plasma drug levels. Besides these PK considerations a significant problem could be nonadherence to drug therapy. In this regard Therapeutic Drug Monitoring (TDM) is a useful tool for detecting nonadherence. Therefore a LC-MS/MS-method for determination of Metoprolol (MET), Amlodipine (AML), Canrenone (CAN) and Hydrochlorothiazide (HCT) was developed. ⋯ Although the level of recommendation of TDM of antihypertensive drugs in patients with refractory hypertension is not yet established, the present LC-MS/MS-method can serve as an effective tool for detection of PK-alterations/nonadherence and may help to monitor antihypertensive pharmacotherapy.