Method of determining risedronate in human plasma based on LC-MS/MS pre-derivatization and application thereof

Abstract

The invention relates to a method of determining risedronate in human plasma based on LC-MS / MS pre-derivatization. The pre-derivatization comprises steps: 150 muL of a plasma sample is taken, 5.00 muLof an internal standard working solution is added, uniform mixing is carried out, 150 muL of 10% trichloroacetic acid is added, after 3 min of oscillation, centrifugation for 5 min at 13,000 rpm is carried out, 100 muL of a supernatant is taken, 57.0 muL of methanol-25% ammonia water (50 to 7, v / v) is added, and 3 min of oscillation is carried out; and 400 muL of trimethylsilyl diazomethane is added, oscillatory derivation for 4 h at 1600 rpm is carried out, and after standing, 2.00 muL of a lower solution is taken for sampling. In comparison with the prior art, a derivative reaction is directly carried out after protein precipitation, the risedronate sample preprocessing process is greatly simplified, and the method has the advantages of short running time, good selectivity and high sensitivity.

Description

technical field [0001] The invention belongs to the technical field of drug analysis, and relates to a method for determining risedronic acid in human plasma based on LC-MS / MS pre-derivatization and an application thereof. Background technique [0002] Risedronate (Risedronate, figure 1 ) is a bisphosphonate compound, which can inhibit the activation of osteoclasts and prevent the dissolution of osteoclasts. It is mainly used clinically for the treatment and prevention of osteoporosis in postmenopausal women. Bisphosphonate drugs can be divided into three generations according to their chemical structure. The representative drugs of the first generation bisphosphonate are etidronic acid and clodronic acid; the second generation bisphosphonate introduces nitrogen atoms in its side chain, representing Drugs include pamidronic acid, alendronic acid, and neridronic acid; the third generation has a cyclic side chain, representing the drugs risedronic acid and zoledronic acid. E...

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Problems solved by technology

[0006] These methods all need to adopt the method of solid phase extraction, and derivatize the bisphosphonic acid compound on the column or after the column, but this method is limited by the solid phase extraction column, need to use the corresponding anion and cation exchange column, Not only is the price expensive, but also in the actual operation process, due to the influence of the pH on the column, the derivatization efficiency will be affected to varying degrees, resulting in poor reproducibility of the method between different laboratories, which affects the further development of bisphosphonate drugs

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