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Plasma estimation of valaciclovir, an antiviral drug, is challenging due to both in-vivo and ex-vivo hydrolysis to active metabolite acyclovir. A simultaneous method is described involving the solid-phase ion-exchange extraction procedure requiring 100 μL of plasma volume, a reverse-phase Lichrosphere RP Select B (125 × 6 mm, 5 μm) column and isocratic mobile phase to achieve the desired chromatographic separation. ESI-MS/MS multiple reaction monitoring in positive polarity, detected mass pairs for valaciclovir (m/z 325.5 → 152.2), acyclovir (m/z 226.3 → 152.2) and respective internal standards valganciclovir (m/z 307.1 → 220.3) and acyclovir-d4 (m/z 230.2 → 152.0). Fully fledged method validation was evaluated as per current regulatory requirements and results were deemed acceptable. The plasma samples showed extensive hydrolysis of valaciclovir when collected or processed at room temperature, without buffer stabilization prior to storage at -15°C. Our results showed that using prechilled K3 EDTA vacutainers immersed in an iced-water bath during blood sample collection, and addition of 50% orthophosphoric acid solution to plasma samples prior to storage at -50°C for at least 120 days controlled the hydrolysis of valaciclovir to acyclovir. While monitoring drug absorption into systematic circulation, the valaciclovir to acyclovir formation ratio was improved to 1:20 in healthy volunteers for the first time.

Aim: A novel and accurate high-throughput tandem mass spectroscopic method has been developed and validated for determination of nifedipine, a calcium-channel blocker. Materials & methods: Nifedipine was detected on a triple quadruple tandem mass spectrometer by multiple reactions monitoring mode via ESI source. Results: The selective and sensitive method was linear in the concentration range of 0.501 to 360.100 ng/ml and reported no matrix effect. The percent accuracy of the method was found to be between 99.7 and 102.80%, while percentage of RSD was in range of 1.77 to 4.73%. Conclusion: Validated method was used for bioavailability studies under fasting and fed conditions. Clinical pharmacokinetics of noncommunicable disease such as hypertension has interested the academicians and practitioners alike due to intricacies and limited knowledge of labile metabolites. Calciumchannel blocker drug slows down the progression of coronary artery calcification. Nifedipine (1,4-dihydro-2, 6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine dicarboxylic acid dimethyl ester), belonging to the group of 1,4-dihydropyridines is one of the highly prescribed calcium-channel blockers that selectively dilates peripheral arteries [1]. It is widely used in the treatment of cardiovascular diseases such as hypertension, angina pectoris and Raynaud's phenomenon [2][3][4]. It inhibits the influx of extracellular calcium through myocardial and vascular membrane pores as well as restricts contractile processes of smooth muscle cells thereby decreasing total peripheral resistance and systemic blood pressure [5,6]. However, developing a robust method for analysis of Nifedipine in plasma is highly challenging due to multiple reasons. Nifedipine is a photo-labile compound, undergoing oxidative biotransformation in human body into pharmacologically inactive metabolites, dehydronifedipine and hydroxydehydro nifedipine carboxylate [7].In recent past, several analytical methods were reported for the determination of nifedipine in biological matrix. These methods include HPLC [8][9][10][11][12][13][14] coupled with UV detectors or electrochemical detector, but tedious sample processing technique, lengthy analysis time and lack of sensitivity were major limitations in these methods. Diverse detection techniques like electron-capture detection [15][16][17][18][19][20], nitrogen phosphorus detection [21] and mass spectrometric (MS) detection [22,23] were reported. However, scope of thermal decomposition of nifedipine under gas chromatography conditions was a co ncern and MS methods are usually preferred.Nifedipine is metabolized by cytochrome P-450 IIIA4 enzymatic activity, in vivo. Nifedipine metabolism involves oxidative dehydrogenation to dehydronifedipine, followed

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