In storing drugs in sealed vials, the gas tightness of the vials often deteriorates due to improper storage methods and substandard product quality, which can easily lead to chemical reactions with various gases in the air and cause deterioration of the drugs and affect their normal use. Therefore, the storage status of drugs can be reflected by measuring the concentration of various gases inside the vials. Among them, water vapor (H2O) is a common gas in the air and is very easy to react with drugs, so the measurement of H2O concentration in medicine bottles is one of the important bases to determine whether the drugs inside the bottles deteriorate. In practice, traditional methods or instruments usually require direct contact with the sample to make a judgment. It is difficult to achieve nondestructive testing, and the sample handling process is tedious, time-consuming and labor-intensive, making it difficult to achieve real-time nondestructive measurement of a large number of drug bottles. In order to efficiently detect and monitor the water vapor concentration in sealed drug storage containers (vials) in real-time, a digital orthogonal phase-locked demodulation algorithm for tunable semiconductor laser absorption spectroscopy (TDLAS) is proposed in this paper, and the feasibility and effectiveness of the algorithm are experimentally verified. The drug bottle is made of transmissive polyethylene (PE) with a length of 12 cm, a width of 9 cm and a height of 64 cm, and a distributed feedback (DFB) laser with a central wavelength of 1 391 nm is used as the light source. The effects of different modulation depths and sampling rates on the amplitude of the demodulated second harmonic signal (WMS-2f) are investigated. The stability of the WMS-2f signal at different optical powers is investigated under the optimal system parameters, and the WMS-2f signal of other unknown water vapor concentrations is deduced from the fitting results. The results show that the digital phase-locked demodulation is more compliable, compact and cheaper than the conventional lock-in amplifier demodulation algorithm. The Allan ANOVA shows that the water vapor detection limit is 18 ppm in the state of 160 s, which verifies the stability and reliability of the method.