Drug design, development and therapy · 2026
An LC-MS/MS Method for Simultaneous Determination of Almonertinib and Atorvastatin: Evaluating Their Drug-Drug Interactions in Rat.
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Li Huanchen, Wu Hongkun, Gao Shouhong, Cui Lili, Xu Jingjie, Sun Jianguo, Liu Zhijun, Wang Zhipeng, Tao Xia
Аннотация
OBJECTIVE: Atorvastatin is frequently used in combination with almonertinib in lung cancer patients who present with comorbid dyslipidemia. Both drugs are metabolized by CYP3A4, potentially leading to drug-drug interactions (DDIs) that increase the risk of adverse reactions. This study aimed to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying almonertinib and atorvastatin and evaluate the DDIs between these two drugs in rats.
METHODS: An LC-MS/MS method was developed to determine almonertinib and atorvastatin in rat plasma and was fully validated in accordance with the ICH M10 bioanalytical method validation guideline and Chinese Pharmacopoeia 2020 Edition. Rats were divided into 5 groups (n=7 per group), and received the following treatments: almonertinib alone, atorvastatin alone, almonertinib combined with atorvastatin, vehicle control, or almonertinib after a long-term regimen of atorvastatin. The plasma samples were collected from each rat and analyzed using this method. The pharmacokinetic parameters were calculated and the DDIs were evaluated.
RESULTS: An LC-MS/MS method was established and validated according to the requirements. Animal studies revealed that co-administration of almonertinib with atorvastatin significantly increased Cmax, AUC0-t, and AUC0-∞ (all p < 0.05), prolonged t1/2 (p < 0.05) and decreased CLz/F, Vz/F (both p < 0.05) of both drugs. Following a 7-day administration of atorvastatin, the DDIs between the two drugs generally weakened, but still differed significantly from those observed with single-drug administration.
CONCLUSION: The study successfully established an LC-MS/MS method for simultaneous determination of almonertinib and atorvastatin and assessed the DDIs of these two drugs in rat. Animal experiment demonstrated significant DDIs between two drugs no matter single dose or multiple doses were administered, which obviously increased the drug exposure and inhibited elimination. Close attention should be paid to the combination regimens of these two drugs in clinical practice.
METHODS: An LC-MS/MS method was developed to determine almonertinib and atorvastatin in rat plasma and was fully validated in accordance with the ICH M10 bioanalytical method validation guideline and Chinese Pharmacopoeia 2020 Edition. Rats were divided into 5 groups (n=7 per group), and received the following treatments: almonertinib alone, atorvastatin alone, almonertinib combined with atorvastatin, vehicle control, or almonertinib after a long-term regimen of atorvastatin. The plasma samples were collected from each rat and analyzed using this method. The pharmacokinetic parameters were calculated and the DDIs were evaluated.
RESULTS: An LC-MS/MS method was established and validated according to the requirements. Animal studies revealed that co-administration of almonertinib with atorvastatin significantly increased Cmax, AUC0-t, and AUC0-∞ (all p < 0.05), prolonged t1/2 (p < 0.05) and decreased CLz/F, Vz/F (both p < 0.05) of both drugs. Following a 7-day administration of atorvastatin, the DDIs between the two drugs generally weakened, but still differed significantly from those observed with single-drug administration.
CONCLUSION: The study successfully established an LC-MS/MS method for simultaneous determination of almonertinib and atorvastatin and assessed the DDIs of these two drugs in rat. Animal experiment demonstrated significant DDIs between two drugs no matter single dose or multiple doses were administered, which obviously increased the drug exposure and inhibited elimination. Close attention should be paid to the combination regimens of these two drugs in clinical practice.