Simultaneous determination of atorvastatin and niacin in human plasma by LC‐MS/MS and its application to a human pharmacokinetic study

Abstract

A rapid, simple, sensitive and selective LC-MS/MS method has been developed and validated for quantification of the atorvastatin (AT) and niacin (NA) in 250 μL human plasma. The analytical procedure involves a liquid-liquid extraction method using nevirapine as an internal standard (IS). The chromatographic separation was achieved on a Hypurity Advance (4.6 × 50 mm, 5 µm) column using a mobile phase consisting of 0.1% formic acid buffer-acetonitrile (20:80, v/v) at flow rate of 0.8 mL/min. The API-4000 LC-MS/MS was operated in the multiple-reaction monitoring mode using electrospray ionization. The total run time of analysis was 3 min and elution of AT, NA and IS occurred at 1.06, 1.84 and 0.92 min, respectively. A detailed validation of the method was performed as per the US Food and Drug Administration guidelines and the standard curves found to be linear in the range of 0.10-30.0 ng/mL for AT and 20.2-6026 ng/mL for NA, with a coefficient of correlation of ≥ 0.99 for both the compounds. AT and NA were found to be stable in a battery of stability studies, viz. bench-top, autosampler, re-injection, wet-extract and repeated freeze-thaw cycles. The developed assay method was successfully applied to a pharmacokinetic study in humans.

A review of chromatographic methods for the determination of water‐ and fat‐soluble vitamins in biological fluids

“…The application of tandem MS allows to increase sensitivity of the HPLC methods even by 1000‐fold when compared with UV detection. LOQ of vitamins of the B group was in the range of 0.5–5 μg/mL for HPLC–UV methods , while measurement using HPLC–MS/MS allowed to obtain LOQ of the range of 1–20 ng/mL . The analytes are determined using an aqueous mobile phase with low organic solvent content.…”

Quantification of Niacin and Its Metabolite Nicotinuric Acid in Human Plasma by LC-MS/MS: Application to a Clinical Trial of a Fixed Dose Combination Tablet of Niacin Extended-Release/Simvastatin (500 mg/10 mg) in Healthy Chinese Volunteers

“…Various methods are available for determination of NA alone or NA along with its metabolites in biological fluids, like determination of NA and its metabolites by LC-MS/MS following deproteinization with acetonitrile in rat or human [ 3 , 12 – 14 ] or with methanol in human or dog [ 5 , 15 ], liquid-liquid extraction with ethyl acetate in human [ 10 , 16 , 17 ], and also solid phase extraction in human [ 2 ]. And also there are some investigations about NA combined with statins drug formulations in animal or humans [ 5 , 11 , 16 , 17 ]. Based on literature survey, we developed a specific LC-MS/MS method for the quantification simultaneously of NA and NUA in human plasma after single dose oral administration of a pharmaceutical formulation containing Simvastatin 10 mg and Niacin 500 mg to healthy Chinese volunteers.…”

Simultaneous determination of plasma creatinine, uric acid, kynurenine and tryptophan by high‐performance liquid chromatography: method validation and in application to the assessment of renal function

“…In addition, UA is also reported to have association with kidney diseases (Bellomo et al ., ; Kutzing and Firestein, ). Kynurenine (KYN) is a metabolite of tryptophan (TRP), an essential amino acid, which plays an important role in protein synthesis and functions as a biochemical precursor for serotonin, niacin and auxin (Koyama et al ., ; Nguyen et al ., ; Pilli et al ., ; Ravi et al ., ; Yubero‐Lahoz et al ., ). Accumulating evidence indicates that blood level of TRP is decreased while KYN is increased in patients with CKD (Saito et al ., ; Zhao, ).…”